Monitoring a neuromuscular blockade status

ABSTRACT

The present disclosure relates to various methods for determining a neuromuscular blockade status and systems suitable for performing such methods. The present disclosure further relates to electro-stimulation electrodes for stimulating a muscle of a patient, optionally in the context of at least some of the mentioned methods. The present disclosure still further relates to hybrid air-signal connectors for use in an electro-stimulation cuff which can be used in the context of at least some of the cited methods. The present disclosure also relates to electro-stimulation circuits comprising an electrode portion and a track portion suitable for pressure cuffs for electro-stimulation, and to pressure cuffs configured to be arranged around a limb of a patient and comprising an active electro-stimulation electrode and a passive electro-stimulation electrode. These electro-stimulation circuits and pressure cuffs may also be used in the context of at least some of the mentioned methods.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application relates to and claims the benefit and priority to U.S.application Ser. No. 15/190,630 filed Jun. 23, 2016, which claims thebenefit and priority to International Application PCT/EP2014/079041filed Dec. 22, 2014, which claims the benefit and priority to SpanishPatent Application Nos. U201331489 filed Dec. 24, 2013 and U201430202filed Feb. 13, 2014.

TECHNICAL FIELD

The present disclosure relates to various methods for determining aneuromuscular blockade status and systems suitable for performing suchmethods.

The present disclosure further relates to electro-stimulation electrodesfor stimulating a muscle of a patient, optionally in the context of atleast some of the above methods.

The present disclosure still further relates to hybrid air-signalconnectors for use in an electro-stimulation cuff which can be used inthe context of at least some of the above methods.

The present disclosure also relates to electro-stimulation circuitscomprising an electrode portion and a track portion suitable forpressure cuffs for electro-stimulation, and to pressure cuffs configuredto be arranged around a limb of a patient and comprising an activeelectro-stimulation electrode and a passive electro-stimulationelectrode.

Throughout the present disclosure, reference is made to “neuromuscularblockade”. In the technical field, neuromuscular blockade may also becalled “neuromuscular block” or “neuromuscular blockage”. The term“neuromuscular blockade” as used herein therefore covers these terms aswell.

BACKGROUND

Neuromuscular transmission may be defined as the transfer of a motorimpulse between a nerve and a muscle in the neuromuscular junction. Thistransmission may be blocked through the use of muscle relaxants. Musclerelaxation may be used during surgery under general anaesthesia to allowe.g. endotracheal intubation and, in general, to provide the surgeonwith the optimum working conditions depending on the type ofintervention.

When muscle relaxants during surgery are used, it is very important tomonitor the patient's neuromuscular blockade status. For such amonitoring, a peripheral motor nerve may be electrically stimulated andmuscle response(s) to said stimulation may be processed to infer theneuromuscular blockade status. In clinical practice, various stimulationpatterns may be used for different purposes and in different phases ofthe operation.

Systems and methods are known based on the above principles. Thesesystems may comprise electrodes for electro stimulating the patient andsensors for detecting a response to the electro-stimulation.

The electrodes may be connected to a provider of electro-stimulationsignals for receiving suitable signals from the provider. The electrodesmay be attached to the skin of the patient at a body part suitable forstimulating a particular motor nerve, such as e.g. ulnar nerve.

The sensors may comprise e.g. an accelerometer attached to e.g. afingertip of the patient for sensing the movement of the finger as areaction to the electro-stimulation. The sensors may be connected to asensing unit in such a way that signals from the sensor(s) are receivedby the sensing unit and processed to generate data representing aresponse to the electro-stimulation.

The electrodes and sensors may therefore be arranged separately ondifferent parts of the body. This dispersion of the electrodes andsensors may make the set-up of the system time-consuming and thesubsequent use of the system cumbersome, which may generate discomfortto the surgical team during surgery. It can even lead to surgeons and/oranaesthesiologists disregarding these systems during surgery.

The provider of electro-stimulation signals and the sensing unit may beintegrated in a single monitor. The electrodes may be connected to themonitor through cables, and the sensors may be connected to the monitorthrough further cables. Therefore, various cables may be present betweenthe patient and the monitor when the electrodes and sensors are attachedto the patient.

Having such a plurality of cables between the monitor and the patientmay be annoying for the surgical staff and may be a source of problemsduring surgery. For example, somebody may accidentally stumble into/overa cable and/or a tangle of cables may occur. This may cause detachmentof an electrode/sensor from the patient and/or disconnection of thecable from the monitor.

U.S. Pat. No. 5,957,860A discloses an apparatus comprising means forstimulating a nerve (e.g. electrodes) and means for detecting a responseto the stimulation. The apparatus is characterized in that said meansare provided in a single body, which is a pressure cuff of the typegenerally used for measuring arterial pressure, provided with orconnected to means for pressure detection. With this apparatus, thepreviously discussed problem about dispersion of electrodes and sensorsis avoided, since they are provided in a single body.

U.S. Pat. No. 5,957,860A further discloses that the pressure cuff andintegrated electrodes may be connected to a monitor through a tubeconfigured to conduct both air and electricity. The monitor may sendsuitable electro-stimulation signals to the electrodes for musclestimulation through said single tube. The monitor may also receivepressure variations in the cuff (representing a response to the musclestimulation) also through said single tube. Hence, the previouslydiscussed problem related to the presence of a plurality of cablesbetween the patient and the monitor is avoided with this configuration.

The monitor may be adapted to receive instructions or parametersprovided by an anaesthesiologist (or similar profile) for the monitor totransmit suitable stimulation signals to the electrodes according tosaid instructions or parameters. For instance, data on stimulationpattern(s) to be used at each time, periodicity of the signals,intensity of the signals, etc. may be provided by the anaesthesiologistto the monitor through suitable data entry means (e.g. a keyboard).

The monitor may also be adapted to receive signals from the sensors(accelerometer, cuff, etc.) and to process them in such a way that arepresentation of them may be provided to a display. This representationof the sensor signals may be displayed in the form of numerical values(e.g. percentages), graphics, etc. in such a way that theanaesthesiologist may derive a muscle response to the performedelectro-stimulation.

It is known that the anaesthesiologist can test (or monitor) aneuromuscular blockade status for a patient by paying attention to thedisplay and manually acting on the monitor depending on the muscleresponses derived from the displayed data. Manually acting on themonitor may comprise providing new instructions/parameters to themonitor in order to cause the transmission of new stimulations signalswith e.g. different intensity, or frequency or stimulation patternsdepending on the new circumstances.

Several iterations of deriving muscle responses (from displayed data)and optionally acting on the monitor may be performed by theanaesthesiologist for finally achieving a target neuromuscular blockadestatus for the patient. This may be labour-intensive, time-consuming andcumbersome for the anaesthesiologist and may generate inefficienciesand/or deficiencies in the process of relaxation (i.e. the initialinduction, subsequent maintenance, and eventual reversal of adrug-induced neuromuscular blockade status) of the patient.

Since the above method of monitoring (or testing) a neuromuscularblockade status highly depends on the attention paid by theanaesthesiologist, a delay between achievement of a neuromuscular statusand corresponding actions on the monitor may occur. Delayed actuationsmay generate inefficiencies in terms of e.g. extending the occupation ofan operating room, using greater amounts of muscle relaxant than reallyneeded, etc.

Furthermore, in an Operating Room, momentary situations of high stressmay exist so that an anaesthesiologist may miss the result of a preciseelectro-stimulation or may lose track of how many stimulations have beenperformed and previous results.

Said dependence on the anaesthesiologist's attention may also cause theanaesthesiologist to act erroneously on the monitor as a consequence ofe.g. a wrong derivation of a muscle response from the displayed data.Wrong actuations by the anaesthesiologist may e.g. generate damage orrisk of damage to the patient, which have to be attenuated duringsurgery. In this case, more surgical resources may be finally used thaninitially required.

In apparatuses based on obtaining or deriving muscle responses dependingon how pressure varies in a pressure cuff (such as e.g. the onedisclosed in U.S. Pat. No. 5,957,860A), patient's heartbeats may createinterferences that may distort the muscle response. Hence, subsequentactions and/or assessments based on said distorted responses maygenerate errors in e.g. monitoring (or testing) a neuromuscular blockadestatus for a patient.

Electro-stimulation electrodes are known for their application on theskin of a patient. These electrodes, which may be suitable forapplications as the ones described before, may comprise a support layerand an electrically conductive material (or medium). The support layermay be made of an electrically insulating material and may be configuredin such a way that, in use, a surface of the support layer contacts theskin of the patient.

The support layer may comprise at least one region having one or moreholes. The electrically conductive medium may be adhered to a surface ofthe support layer which may be the opposite to the surface of contactwith the skin of the patient. The electrically conductive mediumgenerally extends over the holes and a conductive layer is interposed inbetween for conveying current to the skin.

A risk of this structure may be that the conductive layer may be torn ordamaged at the level of the region of contact with the patient's skinand, therefore, the electrically conductive medium may come into directcontact with the skin. In these circumstances, a concentrated andrelatively high current may be transmitted to the patient's skin.

Such a concentration of electrical energy may cause e.g. a burn on theskin of the patient, who may be under general anaesthesia if the patientis being subjected to a surgical operation. In this situation, thepatient may thus not be able to alert the medical team about the damagehe/she is suffering.

Connectors for electro-stimulation cuffs, or compressive armbands, areknown configured to connect a tube for the conveyance of pressurized airto the cuff. These connectors may comprise a body comprising a base anda tubular portion arranged on one face of the base for the coupling ofthe tube.

These connectors may further comprise two connection electrodes havingexternal terminals for connection with external cables, and internalterminals for connection to conductive tracks internal to the cuff. Sucha special type of connectors which feature the ability of simultaneouslyconveying both pressurized air and electrical signals are referredherein as Hybrid Connectors.

Hybrid Connectors for electro-stimulation cuffs should ideally fulfil atleast some of the following requirements:

a) transmission of electrical stimuli emitted from a monitor andconveyed through conductive wires electrically connecting the monitor tothe pressure cuff, for finally discharging the electrical stimuli ontothe patient's skin through corresponding electrodes.

b) entry of pressurized air into the bag of the compressive armbandduring the inflation phase thereof, and subsequent free evacuation ofthe air to e.g. the monitor and, from there, to the atmosphere.

c) pneumatic air tightness of the connection between the inflatable bagand the hybrid connector, without requiring the application of glues,adhesives, or any other type of sealant of chemical nature. A riskassociated with such sealants may be that they can deteriorate over timeand, therefore, air leakages may occur. Moreover, UNE-EN ISO 10.993standards about “Bio-Compatibility of Medical Devices” may not besuitably fulfilled with the use of such sealants.

d) protection against intrusions (of liquids and/or dust) in thejunction between the tube and the hybrid connector. Such intrusions canshort-circuit the conveyance of electrical stimuli which may put at riskthe physical integrity of the patient and/or surgery staff.

e) mechanical resistance of the junction between the tube and the hybridconnector without requiring the application of glues, adhesives, or anyother type of sealant of chemical nature. This requirement is aimed atpreventing that an excessive pulling of the tube (e.g. accidentallyperformed by its unnoticed dragging because of the busy circulation ofthe operation room's staff around the surgical table) could pull out thetube from its receptacle in the hybrid connector.

f) skin friendly nature since the hybrid connector may rest duringsurgery on a delicate skin covering the internal crook of the patient'sarm. With this requirement, e.g. skin lacerations or irritations theretomay therefore be prevented.

U.S. Pat. No. 5,957,860A discloses a pressure cuff with two integratedelectrodes for electro-stimulating a peripheral motor nerve of apatient. The electro-stimulation of the nerve may cause an evoked muscleresponse which may be evaluated in terms of a steep change in the airpressure inside an inflatable bag of the cuff. The magnitude of this airpressure change may determine, by using an appropriate computingalgorithm, an indicator about the neuromuscular blockade status of thepatient.

The electrodes include an active electrode (cathode or negative lead,through which current is supplied) and a passive electrode (anode orpositive lead, through which current is collected). In between theelectrodes, the current passes through a patient's limb, in particular apatient's arm.

FIG. 27a schematically shows a prior art pressure cuff 270 whichcomprises a first electro-stimulation electrode 273 and a secondelectro-stimulation electrode 274. The pressure cuff is shown furthercomprising an inflatable bag 275, and a flexible tube 276 for conductingair and electrical current between the cuff and a monitor or similardevice configured to operate the cuff. As shown in FIG. 27c , thepressure cuff 70 has a length L and a width W.

FIG. 27a also illustrates a theoretical line 271 representing a path ofa nerve to be electro-stimulated through the electrodes 273, 274. Thepressure cuff 270 is configured in such a way that, in use, theelectrodes 273, 274 are arranged on a region of the limb which is atleast partially on or “over” the nerve (theoretically represented by theline 271).

FIG. 27b offers an enlarged view of a region 272 indicated in FIG. 27aand from a point of view 277 also indicated in FIG. 27 a.

As shown in FIG. 27c , the pressure cuff 270 is configured to bepreferentially arranged around a patient's right limb (either arm orleg) with the first and second electrodes 273, 274 and the inflatablebag 275 being suitable arranged according to the following requirements:

The first electrode 273 functions as the anode (or positive lead) and isarranged in a proximal position on an ulnar nerve 278, and the secondelectrode 274 functions as the cathode (or negative lead) and isarranged in a distal position on the ulnar nerve 278. The particularrequirements further comprise the inflatable bag 275 arranged on or overa brachial artery 279.

Pflüger's Law defines the conditions under which an active electrode 274and a passive electrode 273 arranged on a path of a motor nerve 278ensure that an evoked muscle response induced by a current transmittedby the active electrode 274 to the nerve 278 is reliable.

As shown in Table 1, this Law concludes that only when the activeelectrode 274 is in a distal position and the passive electrode 273 isin a proximal position, the evoked muscle response will reliably occurirrespective of the magnitude of the intensity of the currenttransmitted by the active electrode 274.

Herein, distal position refers to a distal position in the correspondingpatient's limb with respect to the patient's trunk, and proximalposition refers to a proximal position in the corresponding patient'slimb with respect to the patient's trunk.

According to Pflüger's Law, an electro-stimulation performed by twoelectrodes 273, 274 placed on a motor nerve 278 can cause an evokedmuscular response (described as “twitch” in Table 1) depending on twoparameters. A first parameter refers to the intensity of the currentgenerated to electro-stimulate the motor nerve 278, and a secondparameter refers to the relative position of the electrodes 273, 274 onthe path of the nerve 278. This second parameter is technically called“polarity”.

Table 1 provides detailed data about this phenomenon. The term ON refersto the moment at which the electrical stimulus is actually applied tothe nerve (closed circuit condition) and the term OFF refers to themoment at which the electrical stimulus is withdrawn (open circuitcondition).

TABLE 1 POLARITY ACTIVE ON ACTIVE ON ELECTRIC PROXIMAL DISTAL CURRENT ONOFF ON OFF WEAK Twitch No twitch Twitch No twitch MEDIUM Twitch TwitchTwitch Twitch STRONG No Twitch Twitch No twitch twitch

In Table 1, three different intensities for the electrical currentapplied for electro-stimulation are considered: WEAK, MEDIUM and STRONG.The content of Table 1 permits deriving that a reliable muscle responsecan be obtained, irrespective of whether the intensity of thestimulating current is WEAK, MEDIUM or STRONG, only when the activeelectrode 274 is arranged in a distal position with respect to thepassive electrode 273, as shown in FIG. 27 c.

However, when the same pressure cuff is changed to a patient's left arm,the practitioner is now forced to rotate the pressure cuff 180° in orderto—as shown in FIG. 27d -match the position of both the stimulatingelectrodes 273, 274 and the inflatable bag 275 with—respectively—thecourse of the peripheral motor nerve 278 and the brachial artery 279 onthe patient's left arm. By doing so, nevertheless, the passive andactive electrodes 273, 274 of the pressure cuff 270 will thenunavoidably be laid out on the motor nerve 278 according to the “ACTIVEON PROXIMAL” arrangement (as identified in Table 1).

As shown in Table 1, such an “ACTIVE ON PROXIMAL” arrangement suffersfrom the important limitation of not being able to warrant an effectiveevoked muscle response (TWITCH) after applying (ON) a stimulatingcurrent of STRONG intensity on the motor nerve.

This electro-physiological phenomenon is technically known as “AnodalBlock of Conduction”, which refers to the lack of evoked muscularresponse featured on a patient's muscle, when the motor nerveinnervating said muscle is stimulated with a high electrical currentintensity using a particular layout of electrodes.

This particular layout comprises the passive electrode (anode, positivelead) of the stimulating circuit placed further distal on the path ofthe motor nerve than the active electrode (cathode, negative lead). Sucha scenario is referred to as “No Twitch” in Table 1, “ACTIVE ONPROXIMAL” Polarity, “ON” column, and “STRONG” Electric Current's row.

Said “Anodal Block of Conduction” has its root in the appearance of apositively charged electrical field under the passive electrode of thestimulating circuit, when said circuit is closed (ON in terms of Table1). The existence of such a positively charged electric field leads tothe so-called hyperpolarization of the nerve's trunk outer membrane. Themagnitude of such a hyperpolarization is directly proportional to thestrength of the positively charged electrical field, which is, in turn,directly proportional to the intensity of the electrical current appliedfor stimulating the nerve.

The propagation of a nervous impulse along a nerve's trunk could beassumed as being a propagation of a negatively charged electrical wavealong the nerve. Therefore, a positively charged electrical fieldanywhere on the nerve's trunk between the active electrode and theinnervated muscle may act as an electrical barrier for the propagationof the cited negatively charged electrical wave. Hence, the positivelycharged electrical field may block, below the passive electrode or anode(this explains the term “Anodal Block”), the eventual arrival of theelectrical nerve impulse to the muscle of interest.

The unnoticed appearance of the “Anodal Block of Conduction” phenomenonmay constitute a potential source of medical errors during theassessment of the neuromuscular blockade condition of a patient,primarily when stimulating a patient's peripheral motor nerve accordingto an “ACTIVE ON PROXIMAL” electrodes' set-up with a STRONG electricalcurrent stimulation intensity. If no muscle response is obtained, theanesthetist may incorrectly diagnose that the patient is in a deepblockade condition whereas the patient might actually be in anon-blocked condition.

Such an observed lack of motor response may actually be caused by theundesired blockade of the nervous signal's propagation at the stronglyhyperpolarized nerve's section under the passive electrode, which may beplaced further distal on the path of the motor nerve which has beenstimulated upstream.

At the current day, the only way to prevent the occurrence of the“Anodal Block of Conduction” phenomenon is to actively invert, throughcorresponding software, the Polarity of the electrodes when the pressurecuff is arranged around a left limb. However, as such a reversaloperation has to be manually carried out by the practitioner on e.g. aconsole, monitor or similar, this solution is not failure proof.

Pressure cuffs incorporating electro-stimulation circuits are known fromU.S. Pat. No. 5,957,860A. Such electro-stimulation circuits may compriseelectrodes and related connections which are made with conventionalelectric components such as e.g. metallic plates for the electrodes andmetallic wires for the connection of the electrodes to a correspondingelectricity source.

This kind of electro-stimulation circuits incorporated in a pressurecuff may be relatively stiff, voluminous, and non-ergonomic, so thatthey may be annoying to the patient to whom the circuit is applied forelectro-stimulation. Moreover, the fabrication of said circuits may becomplicated and time-consuming because a relative large number of manualactions may be required.

The attachment of these electro-stimulation circuits to the pressurecuff may comprise adhesives or similar substances which may causealterations, such as e.g. irritation, of the skin of the patient towhich the circuit is applied for electro-stimulation.

The present disclosure aims at improving upon the prior art methods ofmonitoring a neuromuscular blockade status and systems suitable for suchmethods.

SUMMARY OF THE DISCLOSURE

In a first aspect, a method is provided for automated determination of aneuromuscular blockade status in a patient to whom a muscle relaxant hasbeen delivered. The method is based on a plurality of predefinedneuromuscular blockade status, each of them having predefined one ormore stimulation cycles with a cycle periodicity and one or morecriterions for changing from the neuromuscular blockade status toanother neuromuscular blockade status. The one or more criterionscomprise a first criterion or first set of criterions for changing theneuromuscular blockade status to a first other neuromuscular blockadestatus.

The method comprises automatically performing one or more stimulationcycles predefined for the neuromuscular blockade status, andautomatically determining one or more muscle responses to at least someof the performed stimulation cycles. The method further comprisesautomatically comparing the muscle responses with the predefinedcriterions for changing the neuromuscular blockade status, and, if themuscle responses fulfil the predefined first criterion or first set ofcriterions, then automatically performing one or more stimulation cyclespredefined for the first other neuromuscular blockade status.

The proposed method may be implemented in the form of e.g. a computerprogram which may executable by a suitable system. The aforementioneddrawbacks of the prior art methods may be thus overcome with such anapproach. Derivation of muscle responses and consequent(re)configuration of subsequent stimulation signals may be automaticallyperformed by the method/system without requiring an anaesthesiologist(or similar profile) to pay attention continuously or periodically.

The proposed method may be continuously repeated in such a way thattransitions between different predefined neuromuscular statuses mayautomatically occur until a target predefined neuromuscular status isachieved. Given a current status for the patient, a stimulation cyclepredefined for said current status may be repeated under a periodicitypredefined for said stimulation cycle. Each performed stimulation cyclemay produce a muscle response to said stimulation.

One or more of the last muscle responses may be compared to onecriterion or a set of criterions predefined for the current status. Ifone of the criterions or the set of criterions is fulfilled, theneuromuscular blockade status can be changed from the current status toa new status predefined for the fulfilled criterion. Hence, the currentstatus becomes a previous status whereas the new status becomes thecurrent status. Then, new iterations of the method may be performed forthe “new” current status. And so on until a target neuromuscular status(e.g. unblocked status) is achieved.

The method may further comprise, however, displaying representations ofthe determined muscle responses, such that the anaesthesiologist maytake them into account if desired. The method may also be adapted toreceive manual instructions from the anaesthesiologist aimed atreplacing (possibly temporary) at least some of the “automatic”predefined stimulation cycles, periodicities, criterions, etc.

In some implementations, the one or more criterions for changing fromthe neuromuscular blockade status to another neuromuscular blockadestatus may further comprise a second criterion or second set ofcriterions for one or more of the neuromuscular blockade status. Thesecond criterion or second set of criterions may be predefined forchanging the neuromuscular blockade status to a second otherneuromuscular blockade status. Then, if the muscle responses fulfil saidpredefined second criterion or second set of criterions, one or morestimulation cycles predefined for the second other neuromuscularblockade status may be automatically performed.

Each of the predefined neuromuscular statuses may have associated one ormore stimulation cycles, each of them being predefined according to astimulation pattern, such as e.g. a Single Twitch (ST) pattern, or Trainof Four (TOF) pattern, or Post-tetanic count (PTC) pattern, etc. Moredetailed explanations about these patterns may be provided in otherparts of the description.

Each predefined neuromuscular blockade status may have predefined one ormore stimulation cycles each having predefined a corresponding criterionor set of criterions for changing to another neuromuscular blockadestatus. In an example, an induction status (which means that blockade isbeing induced in the patient) may have predefined a single TOFstimulation cycle and a single (first) criterion or (first) set ofcriterions depending on one or more responses to said TOFstimulation(s).

In another example, a deep status (which means that the patient isconsidered deeply blocked) may have predefined a first stimulation cycleaccording to a TOF pattern, and a second stimulation cycle according toa PTC pattern which is more sensitive than the TOF pattern. In otherwords, the PTC pattern may permit detecting neuromuscular transmissionsthat the TOF pattern cannot detect.

Taking the above into account, a first criterion or first set ofcriterions may be predefined for the TOF stimulation cycle for changingto less deep statuses (e.g. moderate status), and a second criterion orsecond set of criterions may be predefined for the PTC stimulation cyclefor changing to more deep statuses (e.g. intense status). Afterperforming one or more TOF stimulation cycles, if no neuromusculartransmission is detected (or inferred), then the PTC stimulation cycleand the second criterion or second set of criterions may be applied toinfer weaker neuromuscular transmissions and accordingly changing to anew status as predefined in said second criterion or second set ofcriterions.

According to examples, the one or more muscle responses may bedetermined through a pressure cuff applied to a limb of the patient,such that any muscle response has a form of a pressure waverepresentative of how pressure varies over time in the cuff as a resultof said limb's muscle reaction to corresponding performed stimulationcycle(s).

In alternative examples, the one or more muscle responses may bedetermined through other types of sensors. For example, an accelerometer(arranged on e.g. a fingertip of the patient) can be used in the contextof accelerometry methods, and/or force sensors may be used in thecontext of mechanomyography methods.

In a second aspect, a method is provided for determining a muscleresponse to an electro-stimulation of the muscle in a patient, byanalysing the pressure wave in the cuff and filtering the interferencesfrom pressure pulses generated by the heartbeats of the patient. Inparticular, the method comprises determining the end of a heartbeat ofthe patient, and performing the electro-stimulation of the muscle bycausing generation of a first electro-stimulation pulse and,subsequently, one or more further electro-stimulation pulses. The firstelectro-stimulation pulse is generated substantially at the end of theheartbeat.

The method further comprises determining the muscle response in the formof a pressure wave representing how pressure varies over time in apressure cuff as a muscle reaction to the electro-stimulation. Thepressure wave comprises first and further pressure pulses induced by thefirst and further electro-stimulation pulses respectively. The methodalso comprises determining a first characteristic indicative of theshape of the upward slope of the first pressure pulse.

The first characteristic of the upward slope of a pressure pulse may bee.g. the result of dividing the amplitude of the pressure pulse by themaximum derivative of the upward slope.

The method furthermore comprises, for at least some of the furtherpressure pulses, determining the first characteristic of the furtherpressure pulse, determining a deviation between the first characteristicof the further pressure pulse and the first characteristic of the firstpressure pulse, and verifying if the deviation exceeds a deviationthreshold.

The end of the patient's heartbeat may be determined by using any knownsystem/method aimed at inferring a curve representing the heartbeat.This curve may have an upward slope, a peak, and a downward slope. Theend of the heartbeat may be determined when the downward slope of theheartbeat curve substantially ends.

Diverse experiments have revealed that all the pressure pulses (in themuscle response) with amplitude greater than zero have, in the absenceof interferences due to patient's heartbeat, an upward slope with asimilar shape. Generating the first electro-stimulation pulse at the endof a heartbeat may permit assuming that the first pressure pulse(induced by said first electro-stimulation pulse) is free ofinterferences due to patient's heartbeat.

Hence, a deviation between the first characteristic of a furtherpressure pulse and the first characteristic of the first pressure pulse(free of heartbeat interferences) may indicate that the further pressurepulse has been distorted by a heartbeat of the patient. If the deviationis below a deviation threshold, which may indicate that the distortionis substantially small, a correction based on the first characteristicof the first pressure pulse may be applied to the further pressure pulsein order to at least partially eliminate (or attenuate) said distortion.

In case of a negative result of verifying if the deviation exceeds adeviation threshold, an adjustment of the further pressure pulse isperformed. This adjustment is carried out by assuming that the timeuntil peak (or rising time) of the further pressure pulse is measuredcorrectly and that the shape of its upward slope can be described by thefirst characteristic of the first pressure pulse.

In some implementations, in case of a positive result of verifying ifthe deviation exceeds a deviation threshold, an adjustment of thefurther pressure pulse may be performed either based on a firstassumption or on a second assumption. The first assumption may presumethat the time until peak (or rising time) of the further pressure pulseis measured correctly and that the shape of its upward slope can bedescribed by the first characteristic of the first pressure pulse.

The second assumption may presume that the time until peak (or risingtime) of the further pressure pulse is measured correctly and that theshape of its upward slope can be described by substantially subtractinga heartbeat pulse of reference from the measured further pressure pulse.

If the deviation between the first characteristic of the furtherpressure pulse and the first characteristic of the first pressure pulseis above the deviation threshold, which may indicate that the distortionis substantially significant, either a first correction or a secondcorrection may be applied to the further pressure pulse in order to atleast partially eliminate (or attenuate) said distortion.

The first correction may be based on the first characteristic of thefirst pressure pulse, and the second correction may be based onsubstantially subtracting a heartbeat pulse of reference from themeasured further pressure pulse. Either the first or the secondcorrection may be selected depending on the magnitude of the correction.For example, the correction with smaller magnitude may be selected inorder to avoid applying an excessive correction to the further pressurepulse.

The proposed methods may therefore permit determining a “filtered”muscle response without or with smaller distortion(s) due to patient'sheartbeat. These methods may be used in methods based on using anelectro-stimulation cuff as the ones described in other parts of thedescription. These methods may produce more reliable results when usingsaid methods.

In yet a further aspect, an electro-stimulation electrode is providedwhich is configured to be applied dryly (i.e. suitable for its dryapplication) on the skin, preferably intact skin, of a patient. Theconcept of dry application may refer to the application of theelectro-stimulation electrode without the need of applying anyelectrically conductive gel under it.

The electro-stimulation electrode comprises a support layer, anelectrically conductive medium, and a first conductive layer. Thesupport layer is made of an electrically insulating material and has atleast one region with one or more holes. The support layer is arrangedin such a way that, in use, a first surface (or outer surface) of thesupport layer contacts the patient's skin. This outer surface of thesupport layer is therefore aimed at coming into contact with thepatient's skin.

The electrically conductive medium is adhered to a second (or inner)surface of the support layer, opposite to the first surface, andarranged completely or partially surrounding the region with holes insuch a way that the electrically conductive medium does not cover saidregion with holes. In other words, the electrically conductive medium isarranged around the region with holes, such that the electricallyconductive medium completely or partially surrounds said region (withholes) in such a way that the electrically conductive medium does notoverlap with said region (with holes).

The first conductive layer contacts the electrically conductive mediumin such a way that the first conductive layer covers (or overlaps with)the region with holes.

The suggested electro-stimulation electrode substantially eliminates therisk of causing burns on the patient's skin. This effect is achievedbecause the electrical current is transmitted to the patient's skinthrough the one or more holes (of the support layer) from surroundingpositions, since the electrically conductive medium (completely orpartially) surrounds said region with holes. Therefore, the electricalcurrent conveyed by the electrically conductive medium cannot reach theskin of the patient directly from the electrically conductive mediumitself.

In yet another aspect, a hybrid air-signal connector is provided forconnecting an air-signal tube to an electro-stimulation cuff. The hybridair-signal connector is therefore aimed at connecting theelectro-stimulation cuff with a tube of introduction of pressurized airand electrical pulse. The electro-stimulation cuff may have innerconductive tracks and a connection bore, and the air-signal tube mayhave an air conduit and electrically conductive cables.

The hybrid air-signal connector comprises a main body and two connectionelectrodes. The main body has a base with a first tubular portionarranged on a first face of the base in such a way that, in use, thefirst tubular portion is fitted into the air conduit of the air-signaltube such that air can flow between the air conduit and the inside ofthe cuff through the first tubular portion. In other words, the mainbody comprises a base from whose centre a tubular portion extends on oneside, so-called outer side, the tubular portion being for coupling ofthe tube.

The two connection electrodes may be either L-shaped or substantiallyflat.

The connection electrodes have external terminals (for connection withexternal cables) and internal terminals (for connection with conductivetracks internal to the cuff).

In the case of the L-shaped electrodes, the external terminals extendfrom the base parallel (and optionally contiguously) to the firsttubular portion in such a way that, in use, each external terminalcontacts one of the electrically conductive cables of the air-signaltube.

In the case of the substantially flat electrodes, the external terminalsare embedded in the base with an end portion arranged on the first faceof the base in such a way that, in use, this end portion contacts anelectrically conductive cable of the air-signal tube.

The internal terminals (of either L-shaped or substantially flatelectrodes) are embedded in the base with an end portion arranged on thefirst face of the base in such a way that, in use, the end portioncontacts one of the inner conductive tracks of the cuff when the hybridair-signal connector is introduced into the connection bore of the cuff.In other words, the internal terminals are embedded in the base withtheir ends exposed on the outer side of the base, so that said ends comeinto contact with the tracks when the hybrid air-signal connector isintroduced into a connection bore of the cuff.

The proposed hybrid air-signal connectors permit a relatively effectiveconnection of an air-signal tube to an electro-stimulation cuff. Arelatively effective connection of the wires comprised in the air-signaltube to the inner conductive tracks of the cuff can be effectivelyimplemented through said hybrid air-signal connector as a result of theparticular configuration and arrangement of its connection electrodes.

The hybrid air-signal connector may also permit an effective air flowbetween the tube and the cuff when the first tubular region of theconnector is fitted into the air conduit of the tube. Suitable pneumaticair tightness, protection against intrusions of liquids and/or dust,mechanical resistance against sudden pulling efforts and a skin friendlynature may also be provided by the said hybrid air-signal connector ife.g. a proper material is chosen for its manufacturing.

In a yet further aspect, a pressure cuff is provided configured to bearranged around a limb of a patient and comprising an activeelectro-stimulation electrode and a passive electro-stimulationelectrode.

The active electro-stimulation electrode (cathode or negative lead) isconfigured to transmit an electrical current and is arranged in thepressure cuff in such a way that, in use, a contact surface of theactive electro-stimulation electrode is arranged on a first region ofthe limb, which is at least partially on a peripheral motor nerve of thelimb such that the nerve receives at least part of the transmittedelectrical current.

The passive electro-stimulation electrode (anode or positive lead) isconfigured to collect an electrical current and is arranged in thepressure cuff in such a way that, in use, a contact surface of thepassive electro-stimulation electrode is arranged on a second region ofthe limb, such that the transmitted electrical current is collected bythe passive electro-stimulation electrode.

The second region of the limb is not on the peripheral motor nerve,and/or the contact surface of the passive electro-stimulation electrodeis substantially larger in size than the contact surface of the activeelectro-stimulation electrode.

The proposed pressure cuff may be used for assessing the drug-inducedneuromuscular blockade condition of an anesthetized patient, bymeasuring the strength of an evoked muscular response obtained from thecuff as a result of electro stimulating the peripheral motor nerve.

This strength of the evoked muscular response may be determined bymeasuring, with the use of an appropriate computing algorithm, themagnitude of the air pressure peak that occur inside an inflatable bagof the cuff on each muscular motor response.

As described in other parts of the description, a phenomenon known as“Anodal Block of Conduction” may block the propagation of a nerveimpulse induced by the electro-stimulation, which may cause the absenceof evoked muscular response. The unnoticed appearance of the “AnodalBlock of Conduction” phenomenon may constitute a potential source ofmedical errors during the assessment of the neuromuscular blockadecondition of a patient.

With the proposed pressure cuff, the potential risk of incorrectlyassessing the neuromuscular blockade condition of a patient because ofthe unnoticed event of the “Anodal Block of Conduction” phenomenon issubstantially reduced or even eliminated.

If the proposed pressure cuff is arranged on either the right or leftarm of the patient with the passive electrode in a proximal positionwith respect to the active electrode, a reliable evoked muscle responsewill always occur according to Pflüger's Law. This principle isirrespective of whether the passive electrode is arranged on the motornerve's course or not, and of whether the passive electrode is larger insize than the active electrode or not.

With the proposed pressure cuff, regardless of whether it is arranged oneither the right or left arm of the patient, and even with the passiveelectrode in a distal position with respect to the active electrode, areliably evoked muscle response will also occur:

If the passive electrode (even if in the distal position) is notarranged on the motor nerve's course, the risk of blockade of the normalpropagation of nerve impulses along said nerve's trunk due to theunnoticed appearance of the “Anodal Block of Conduction” phenomenon maybe non-existent. This is because the passive electrode (in the distalposition) is placed outside the area of influence of the motor nerve, sothat no hyperpolarization of the outer membrane of the nerve may beinduced by the passive electrode. Such an avoidance of the risk ofunnoticed blockade of the propagation of nerve impulses is irrespectiveof the size of the contact surface of the passive electrode (in thedistal position) with the patient's skin.

If the passive electrode (in the distal position) is arranged on themotor nerve's course and its contact surface with the patient's skin hasa size larger than the contact surface of the active electrode, the riskof blocking the normal propagation of nerve impulses along the nerve'strunk due to the unnoticed appearance of the “Anodal Block ofConduction” phenomenon, may also be relatively low or even non-existent.This is because the larger size of the passive electrode acts as adiffuser which effectively reduces the density of electrical currentexisting at any point of the said contact surface of the passiveelectrode with the patient's skin. As a consequence, this low density ofelectrical current also creates a relatively weak positively chargedelectrical field under said contact surface which in turn, induces arelatively low hyperpolarization level on the outer membrane of themotor nerve's trunk. Hence the risk of appearance of the “Anodal Blockof Conduction” phenomenon is significantly reduced or even eliminated.

In some examples, the second region of the limb may be at leastpartially on the peripheral motor nerve of the limb, and the contactsurface of the passive electro-stimulation electrode may besubstantially larger in size than the contact surface of the activeelectro-stimulation electrode. In some particular examples, the contactsurface of the passive electro-stimulation electrode may substantiallycompletely surround the contact surface of the activeelectro-stimulation electrode in a, for example, substantially coaxialmanner.

An advantageous aspect of having the active electrode completelysurrounded by the larger passive electrode may be that the electricalprotection of the patient's heart may be improved. This is based on thatthe larger contact surface of the passive electrode constitutes aneffective and preferential exit for the electro-stimulation current, sothat said current does not flow towards the patient's heart. Thisconclusion may be further based on that such a preferential exit for theelectro-stimulation current covers the entire 360 degrees around theactive electrode.

In some examples wherein the passive electrode is larger than the activeelectrode, the contact surface of the passive electro-stimulationelectrode may partially surround the contact surface of the activeelectro-stimulation electrode. For example, the passiveelectro-stimulation electrode may be substantially C-shaped. In otherexamples, the passive electro-stimulation electrode may be formed as twoannular segments, each having a first end and a second end, the firstends facing each other with a first gap in between and the second endsfacing each other with a second gap in between.

An aspect of these last configurations (C-shaped and those based onannular segments) may be that they also benefit from the diffusingeffect of the electrical current density explained before. Hence, therisk of appearance of the “Anodal Block of Conduction” phenomenon issignificantly reduced or even eliminated. Moreover, the passiveelectrode may also constitute an effective and preferential exit for theelectro-stimulation current, covering the almost entire 360 degreesaround the active electrode, which may improve the electrical protectionof the patient's heart.

Any of the previous configurations of active and passive electrodesdescribed in the context of pressure cuffs may be implemented based onthe features and principles described in other parts of the descriptionwith respect to electro-stimulation circuits formed as a singlemultilayer film.

In a yet another aspect, electro-stimulation circuits are providedcomprising an electrode portion and a track portion. The electrodeportion is configured to either transmit or collect an electricalcurrent to/from a region of a patient's skin for electro-stimulating aperipheral motor nerve of the patient. The track portion is configuredto conduct the electrical current to/from the electrode portion. Theelectrode and track portions are integrally formed as a singlemultilayer film having a plurality of layers.

The plurality of layers comprises a first layer and a second layerattached to each other. The first layer may be made of thermoplasticpolymer, such as e.g. Thermoplastic polyurethane (TPU) and/or Polyvinylchloride (PVC), doped with electrically conductive particles, such ase.g. graphite particles. The second layer may be made of electricallyconductive material, such as e.g. an electrically conductive fabricwhich may comprise carbon fibre and/or a metallic mesh.

The proposed electro-stimulation circuits may be fabricated in wayswhich can be easily scaled up. They may be manufactured in single-stepmanufacturing processes such as thermal continuous lamination. Besides,these electro-stimulation circuits may subsequently be easily adhered toa pressure cuff cover without the need of using adhesives or similarsubstances, thanks to the welding properties of the thermoplasticpolymer of the first layer.

The first layer may permit skin friendly transmissions of electricitybetween the electrode portion and a target region of the patient's skinfor stimulating a nerve. The second layer may provide efficientelectrical conductivity properties to the track portion for conductingelectricity to/from the electrode portion of the circuit.

In some examples, the plurality of layers may further comprise a thirdlayer of thermoplastic polymer attached to the second layer in such away that the second layer is sandwiched between the first layer and thethird layer. This third layer may be made of thermoplastic polymer dopedwith electrically conductive particles.

According to examples, the layers of the plurality of layers may beattached together with a heated lamination process. This process may bea single step process, which may therefore make the fabrication of theelectro-stimulation circuits less complicated and less time-consuming incomparison with other manufacturing processes such as e.g.layer-by-layer deposition of thin films (used e.g. in PrintedElectronics and/or Phase-Vapour Deposition technologies).

In addition, since the abovementioned lamination process is a continuousmanufacturing process, it also provides benefits in terms of costsavings derived from the economies of scale. More detailed argumentationis provided in other parts of the description.

In examples, a pressure cuff may be provided which may be configured tobe arranged around a limb of a patient and may comprise at least one ofthe previous electro-stimulation circuits. The electro-stimulationcircuit may be attached to the pressure cuff in such a way that, in use,a contact surface of the electrode portion of the electro-stimulationcircuit is arranged on a region of the limb such that an electricalcurrent can be either transmitted or collected by the electrode portionto/from said region of the limb for electro-stimulating a peripheralmotor nerve.

The attachment of the electro-stimulation circuit to the pressure cuffmay comprise an attachment of a layer of the electro-stimulation circuitmade of thermoplastic polymer to a region of the pressure cuff also madeof thermoplastic polymer. For example, the pressure cuff may comprise afabric cover having a layer made of thermoplastic polymer to which thelayer of thermoplastic polymer of the electro-stimulation circuit may beattached. This fabric cover may comprise a further layer made of nylon,paper or nonwoven fabric attached to the layer of thermoplastic polymerthrough e.g. a heated lamination process.

Such a layer of nylon, paper or nonwoven fabric may be an outer layer ofthe fabric cover and the layer of thermoplastic polymer may be an innerlayer of the fabric cover, such that a relatively compact and resistantpressure cuff may be obtained. The outer layer of nylon, paper ornonwoven fabric may generally attribute enough strength to the cuff,whereas the inner layer of thermoplastic polymer may permit a relativelystrong attachment of the electro-stimulation circuit(s) to the cuff.This may also contribute to make the inflatable bag of the pressure cuffleak-proof.

The attachment between the thermoplastic polymer layer of the circuit(s)and the thermoplastic polymer layer of the fabric cover may beimplemented with a welding process. This welding process may be e.g. ahot plate welding process or an ultrasound welding process or a radiofrequency welding process. An advantageous aspect of using a radiofrequency welding process may be that it may effectively avoid theappearance of creases, fissures and/or deformations on the outer surfaceof the materials to be welded. This advantage is due to that the radiofrequency welding process only applies heat at the specific contactinterface between the two layers to be welded, while keeping the rest ofsaid layers at room temperature.

Any of the previous electro-stimulation circuits formed as a singlemultilayer film and related principles may be used for fabricating anyof the pressure cuffs with an active electro-stimulation electrode and apassive electro-stimulation electrode described in other parts of thedescription.

BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting examples of the present disclosure will be described in thefollowing, with reference to the appended drawings, in which:

FIG. 1 is a flow chart schematically illustrating automatic changes frominduction status to other statuses in a method for automateddetermination of a neuromuscular blockade status in a patient accordingto a first example;

FIG. 2 is a flow chart schematically illustrating automatic changes frommoderate status to other statuses in the context of a method accordingto the same or similar example;

FIG. 3 is a flow chart schematically illustrating automatic changes fromdeep status to other statuses in the context of a method according tothe same or similar example;

FIG. 4 is a flow chart schematically illustrating automatic changes fromintense status to other statuses in the context of a method according tothe same or similar example;

FIG. 5 is a flow chart schematically illustrating automatic changes fromreversion status to other statuses in the context of a method accordingto the same or similar example;

FIG. 6 is a flow chart schematically illustrating automatic changes fromend-of-reversion status to other statuses in the context of a methodaccording to the same or similar example;

FIG. 7 is a flow chart schematically illustrating initial andcalibration phases in the context of a method according to the same orsimilar example;

FIG. 8 is a flow chart schematically illustrating a sub-method of amethod according to another example assuming that a “faster reversion”drug has been delivered to the patient;

FIG. 9 schematically shows a pressure pulse due to a patient's heartbeatand related parameters, the pressure pulse being obtained through apressure cuff;

FIG. 10 schematically shows a muscle response pulse due to an electrostimulation pulse and related parameters, the muscle response pulsebeing obtained through a pressure cuff;

FIGS. 11 and 12 schematically shows respective views of a muscleresponse pulse due to an electro stimulation pulse and a heartbeat pulseinterfering with the muscle response pulse, both pulses being obtainedthrough a pressure cuff;

FIG. 13 schematically shows a sequence of heartbeat pulses and a muscleresponse to a TOF stimulation, both the heartbeat pulses and muscleresponse pulses being obtained through a pressure cuff;

FIG. 14 is a flow chart schematically illustrating a method ofdetermining a muscle response to an electro-stimulation, according toexam pies;

FIG. 15 is a flow chart schematically illustrating an implementation ofa block comprised in the flow chart of FIG. 14, according to examples;

FIG. 16a is an exploded perspective view of an electro-stimulationelectrode according to a first example;

FIGS. 16b to 16e are cross-sectional views of the electro-stimulationelectrode according to the first example;

FIG. 17a is an exploded perspective view of an electro-stimulationelectrode according to a second example;

FIGS. 17b to 17g are cross-sectional views showing the steps ofassembling the electro-stimulation electrode according to a secondexample;

FIG. 18 is a perspective cross-sectional view of a hybrid air-signalconnector according to an example;

FIG. 19 is a top perspective view of the air-signal hybrid connector;

FIG. 20 is a bottom perspective view of the hybrid air-signal connector;

FIG. 21 is a cross-sectional view of the hybrid air-signal connector;

FIG. 22 is a plan view of the hybrid air-signal connector;

FIG. 23 is a perspective view of a cuff and a hybrid air-signal tubeconnected to the cuff through the hybrid air-signal connector;

FIG. 24 is a bottom perspective view of the hybrid air-signal connectorwhich is being fitted into a connection bore of the cuff at an innerside of the cuff's fabric cover;

FIG. 25 is a top perspective view of a hybrid air-signal connectoraccording to a further example;

FIG. 26 is a cross-sectional view of the hybrid air-signal connector ofFIG. 25;

FIG. 27a schematically illustrates a perspective view of an example ofprior art pressure cuff with electro-stimulation electrodes;

FIG. 27b schematically illustrates a region of the pressure cuff of

FIG. 27a taken from a point of view indicated in FIG. 27 a;

FIG. 27c schematically illustrates a prior art pressure cuff positionedin accordance with its correct arrangement around a patient's right arm;

FIG. 27d schematically illustrates the pressure cuff of FIG. 27cpositioned in accordance with its correct arrangement around a patient'sleft arm;

FIG. 28a-28c schematically illustrate respective views similar to theone shown in FIG. 27b but with different configurations of electrodesaccording to respective examples;

FIG. 29a-29b schematically illustrate respective views similar to theones shown in FIGS. 28a-28c but with different configurations ofelectrodes according to respective other examples;

FIG. 30a schematically illustrates a sectional view of a portion of alaminated base material suitable for constructing electro-stimulationcircuits according to an example;

FIG. 30b schematically illustrates a sectional view of a portion ofanother laminated base material suitable for constructingelectro-stimulation circuits according to another example;

FIG. 30c schematically illustrates a process of fabricating a laminatedbase material similar to the ones shown in FIGS. 30a and 30 b;

FIG. 31a schematically illustrates a pressure cuff comprisingelectro-stimulation circuits according to examples;

FIG. 31b schematically illustrates an enlarged view of a region of apressure cuff similar to the one depicted in FIG. 31a , whereinconfiguration details about the electro-stimulation circuits are shown;and

FIG. 32 schematically illustrates a cross sectional view of a pressurecuff region similar to the one shown in FIG. 31b , said view having beentaken according to a plane indicated in FIG. 31 b.

DETAILED DESCRIPTION

FIGS. 1 to 8 are flow charts schematically illustrating automatictransitions between statuses in the context of methods for automateddetermination of a neuromuscular blockade status for a patient. Duringsurgery, depending on the circumstances, the neuromuscular transmissionmay be blocked by delivering a muscle relaxant to the patient and saidblockade may be reverted by delivering to the patient a drug aimed atthat end.

Methods are based on having predefined a plurality of neuromuscularblockade statuses, each having predefined one or more stimulation cycleswith a cycle periodicity and one or more criterions for changing theneuromuscular blockade status to another neuromuscular blockade status.

Examples of predefined neuromuscular statuses may be e.g. inductionstatus, moderate status, deep status, intense status, reversion status,and end-of-reversion status. Unblocked status may be a “fictitious”status indicating that some ending condition has arisen, which may causeending of the method.

Induction status may refer to that a muscle relaxant has been deliveredto the patient and affectation of the muscle relaxant is in progresstowards a desired neuromuscular blockade.

Moderate status may refer to that a neuromuscular blockade has beenachieved which is not very high, so that some response(s) to TOF(train-of-four) stimulation(s) may occur, such as e.g. TOF-count between1 and 3.

Deep status may refer to that a neuromuscular blockade has been achievedwhich is higher, so that no response(s) to TOF stimulation(s) can beobtained but some response(s) to PTC (post-tetanic count) stimulation(s)may occur.

Intense status may refer to that a neuromuscular blockade has beenachieved which is very intense, so that no response(s) to any type ofstimulation(s), either TOF or PTC stimulation(s), can be obtained.

Reversion status may refer to that the neuromuscular blockade is beingreverted by e.g. delivering to the patient a drug aimed at that purpose.This drug may be a “standard reversion” drug or a “faster reversion”drug. More details about said types of drugs are provided in other partsof the description.

These statuses are well defined in medical literature.

End-of-reversion status may refer to that reversion of the neuromuscularblockade is close to its end, so that the method may be ended when apredefined ending condition (based on e.g. TOF stimulation(s)) isfinally satisfied.

The one or more predefined stimulation cycles may comprise one or morestimulation cycles according to a Single Twitch (ST) pattern based ongenerating a single ST stimulation pulse. In this case, a muscleresponse to a performed ST stimulation cycle may comprise a single STresponse pulse induced by the ST stimulation pulse.

A ST-ratio parameter may be inferred from a ST muscle response, saidST-ratio corresponding to the percentage of the ST response pulse withrespect to a ST response pulse of reference determined before deliveringthe muscle relaxant to the patient. Since ST patterns are well known inmonitoring neuromuscular blockade, no further details will be providedto this respect.

The one or more predefined stimulation cycles may comprise one or morestimulation cycles according to a Train of four (TOF) pattern. A TOFpattern may be based on generating first, second, third and fourth TOFstimulation pulses with a frequency of 2 Hz. A muscle response to aperformed TOF stimulation cycle may thus have first, second, third andfourth TOF response pulses induced by the first, second, third andfourth TOF stimulation pulses respectively.

A TOF-count parameter and a TOF-ratio parameter may be inferred from aTOF muscle response. The TOF-count parameter may correspond to thenumber of TOF response pulses with amplitude greater than zero in theTOF muscle response. The TOF-ratio parameter may correspond to thepercentage of the fourth TOF response pulse with respect to the firstTOF response pulse.

Since TOF patterns are well known in monitoring neuromuscular blockade,no further details will be provided to this respect.

The one or more predefined stimulation cycles may comprise one or morestimulation cycles according to a Post-tetanic count (PTC) pattern basedon a tetanus stimulation during between 2 and 8 seconds (e.g. 5seconds), followed by a period of single twitch (ST) pulses of between10 and 20 seconds (e.g. 15 seconds).

A muscle response to a performed PTC stimulation cycle may have PTCresponse pulses induced by the ST pulses of the PTC stimulation cycle.

A PTC-count parameter may be derived from a PTC muscle response, saidPTC-count parameter corresponding to the number of PTC response pulseswith amplitude greater than zero in the PTC muscle response. Since PTCpatterns are well known in monitoring neuromuscular blockade, no furtherdetails will be provided to this respect.

FIG. 1 is a flow chart schematically illustrating automatic changes froma predefined induction status 100 a to other statuses 100 b, 100 d in amethod being performed for a patient to whom a muscle relaxant has beendelivered. Induction status 100 a may be initially attributed to thepatient by default (e.g. after delivery of the muscle relaxant) ordepending on a previous phase 1PREV.

This previous phase 1PREV may be e.g. an initial or calibration phase,examples of which may be provided in other parts of the description.

The induction status 100 a may have predefined a TOF stimulation cyclewith a cycle periodicity of e.g. 12 seconds. At block 1 a, the methodmay therefore comprise waiting for 12 seconds and then, once the 12seconds have elapsed, proceeding to block 1 b. At block 1 b, performanceof the predefined TOF stimulation cycle may be caused along withderivation of corresponding TOF-count and TOF-ratio parameters.

The induction status 100 a may also have predefined a first criterion orfirst set of criterions for changing the neuromuscular status. Thisfirst criterion or first set of criterions is described below withreference to blocks 1 c-1 f of FIG. 1.

At block 1 c, a verification of whether TOF-count is less than 4 may beperformed. In case of a positive result of said verification, theneuromuscular status may be changed to moderate status 100 b. In case ofa negative result of said verification, the method may continue to block1 d.

At block 1 d, a verification of whether TOF-ratio is less than 30% maybe performed. In case of a positive result of said verification, themethod may proceed to block 1 e. In case of a negative result of saidverification, the method may continue to block 1 f.

At block 1 e, the method may comprise verifying whether TOF-ratio hasbeen less than 30% during 5 minutes. In case of a positive result ofsaid verification, the neuromuscular status may be changed to moderatestatus 100 b. In case of a negative result of said verification, themethod may loop back to block 1 a for initiating a new iteration of theTOF stimulation cycle (block 1 b) and verification of the firstcriterion or first set of criterions (blocks 1 c-1 f).

In certain surgical procedures, a relatively low level of neuromuscularblockade (or partial neuromuscular blockade) may be required, such thatfourth TOF response pulses may have amplitude greater than zeropermanently. In such circumstances, TOF-count would be equal to 4 andTOF-ratio would be greater than 0% always.

The above transition, at block 1 e, from induction status 100 a tomoderate status 100 b when TOF-ratio has been less than 30% during 5minutes is aimed at properly monitoring said partial neuromuscularblockade. More details about partial neuromuscular blockade in thecontext of methods are provided in other parts of the description.

At block 1 f, the method may comprise verifying whether TOF-ratio hasbeen greater than or equal to 30% during 15 minutes. In case of apositive result of said verification, the neuromuscular status may bechanged to unblocked status 100 d. In case of a negative result of saidverification, the method may loop back to block 1 a for initiating a newiteration of the TOF stimulation cycle (block 1 b) and verification ofthe first criterion or first set of criterions (blocks 1 c-1 f).

When unblocked status 100 d is attributed to the patient, the method mayend its execution as it may be considered that the patient's muscles arenot blocked anymore.

Alternatively to the previously described TOF stimulation cycle andfirst criterion or first set of criterions, the transition frominduction status 100 a to moderate status 100 b may be based on a STstimulation cycle and a corresponding first criterion (or first set ofcriterions). The periodicity of said ST stimulation cycle may be ofapproximately 1 second, and the first criterion (or first set ofcriterions) may be based on the following rule.

A first counter may be increased by a single unit when ST-ratio is lessthan or equal to 15%. This first counter may be increased by anadditional unit when ST-ratio is less than or equal to 8%. A secondcounter may be increased by a single unit when ST-ratio is less than orequal to 4%.

The first and second counters may be set to zero when three consecutiveST stimulations with ST-ratio greater than 15% occur. The neuromuscularblockade status may be changed to moderate status 100 b when the firstcounter is greater than or equal to 20 and the second counter is greaterthan or equal to 3.

FIG. 2 is a flow chart schematically illustrating automatic changes frommoderate status 100 b to other statuses in the same or in a similarmethod. Moderate status 100 b may be attributed to the patient dependingon a previous phase 2PREV.

This previous phase 2PREV may be the “induction phase” 100 a describedin relation to FIG. 1, for example. Other possible transitions tomoderate status 100 b are described in other parts of the description.

The moderate status 100 b may have a predefined TOF stimulation cyclewith a cycle periodicity of e.g. 1 minute. At block 2 a, the method maytherefore comprise waiting for 1 minute and then proceeding to block 2b. At block 2 b, performance of the predefined TOF stimulation cycle maybe caused along with derivation of corresponding TOF-count and TOF-ratioparameters.

The moderate status 100 b may also have predefined a first criterion orfirst set of criterions for changing the neuromuscular status. Thisfirst criterion or first set of criterions is described below withreference to blocks 2 c-2 g of FIG. 2.

At block 2 c, a verification of whether the TOF-count is equal to zeroand the TOF-ratio is equal to 0% may be performed. In case of a positiveresult of said verification, the method may proceed to block 2 d. Incase of a negative result of said verification, the method may continueto block 2 f.

At block 2 d, a counter of consecutive TOF stimulations with a TOF-countequal to zero and a TOF-ratio equal to 0% may be increased and,afterwards, the method may continue to block 2 e.

At block 2 e, the method may comprise verifying whether the counter ofconsecutive TOF stimulations with TOF-count equal to zero and TOF-ratioequal to 0% is equal to 2. In case of a positive result of saidverification, the neuromuscular status may be changed to deep status 100e. In case of a negative result of said verification, the method mayloop back to block 2 a.

At block 2 f, a verification of whether TOF-ratio is greater than orequal to 80% may be performed. In case of a positive result of saidverification, the neuromuscular status may be changed toend-of-reversion status 100 h. In case of a negative result of saidverification, the method may continue to block 2 g.

At block 2 g, a verification of whether TOF-ratio is greater than orequal to 4% may be performed. In case of a positive result of saidverification, the neuromuscular status may be changed to reversionstatus 100 g. In case of a negative result of said verification, themethod may loop back to block 2 a.

At blocks 2 f and 2 g, the determination is made whether the patient'smuscles are becoming unblocked or have already become significantlyunblocked.

FIG. 3 is a flow chart schematically illustrating automatic changes fromdeep status 100 e to other statuses in the same or in a similar method.Deep status 100 e may be attributed to the patient depending on aprevious phase 3PREV.

This previous phase 3PREV may be the “moderate phase” 100 b described inrelation to FIG. 2.

The deep status 100 e may have predefined a TOF stimulation cycle with acycle periodicity of e.g. approximately 2 minutes. At block 3 a, themethod may therefore comprise waiting for 2 minutes and then proceedingto block 3 b. At block 3 b, performance of the predefined TOFstimulation cycle may be caused along with derivation of correspondingTOF-count and TOF-ratio parameters.

The deep status 100 e may also have a predefined first criterion orfirst set of criterions for changing the neuromuscular status. Thisfirst criterion or first set of criterions is described below withreference to blocks 3 c-3 e and 3 h-3 j of FIG. 3.

At block 3 c, a verification of whether a TOF-count is equal to zero anda TOF-ratio is equal to 0% may be performed. In case of a positiveresult of said verification, the method may proceed to block 3 d. Incase of a negative result of said verification, the method may continueto block 3 h.

At block 3 h, a verification of whether TOF-ratio is greater than orequal to 80% may be performed. In case of a positive result of saidverification, the neuromuscular status may be changed toend-of-reversion status 100 h. In case of a negative result of saidverification, the method may continue to block 3 i.

At block 3 i, a verification of whether TOF-ratio is greater than orequal to 7% may be performed. In case of a positive result of saidverification, the neuromuscular status may be changed to reversionstatus 100 g. In this sense, the blocks 3 h and 3 i are generallycomparable to blocks 2 f and 2 g for a different neuromuscular blockadestatus.

In case of a negative result of the verification in block 3 i, themethod may continue to block 3 j.

At block 3 j, a verification of whether a TOF-count is greater than zeromay be performed. In case of a positive result of said verification, theneuromuscular status may be changed to moderate status 100 b. In case ofa negative result of said verification, the method may loop back toblock 3 a.

At block 3 d, a counter of consecutive TOF stimulations with TOF-countequal to zero and TOF-ratio equal to 0% may be increased and,afterwards, the method may continue to block 3 e.

At block 3 e, the method may comprise verifying whether the counter ofconsecutive TOF stimulations with TOF-count equal to zero and TOF-ratioequal to 0% is equal to 3. In case of a positive result of saidverification, the method may continue to block 3 f. In case of anegative result of said verification, the method may loop back to block3 a.

The deep status 100 e may further have predefined a PTC stimulationcycle with a cycle periodicity of e.g. approximately 6 minutes. At block3 f, the method may comprise waiting for 12 seconds after TOFstimulation and then causing performance of the predefined PTCstimulation cycle along with derivation of corresponding PTC-countparameter.

The deep status 100 e may also have predefined a second criterion orsecond set of criterions for changing the neuromuscular status. Thissecond criterion (or second set of criterions) is described below withreference to block 3 g of FIG. 3.

At block 3 g, a verification of whether PTC-count is less than or equalto 4 may be performed. In case of a positive result of saidverification, the neuromuscular status may be changed to intense status100 f. In case of a negative result of said verification, the method mayloop back to block 3 a.

FIG. 4 is a flow chart schematically illustrating automatic changes fromintense status 100 f to other statuses in the same or in a similarmethod. Intense status 100 f may be attributed to the patient dependingon a previous phase 4PREV.

This previous phase 4PREV may be the “deep phase” 100 e described inrelation to FIG. 3, for example.

The intense status 100 f may have a predefined TOF stimulation cyclewith a cycle periodicity of e.g. approximately 2 minutes. At block 4 a,the method may therefore comprise waiting for 2 minutes and thenproceeding to block 4 b. At block 4 b, performance of the predefined TOFstimulation cycle may be caused along with derivation of correspondingTOF-count and TOF-ratio parameters.

The intense status 100 f may also have predefined a first criterion orfirst set of criterions for changing the neuromuscular status. Thisfirst criterion (or first set of criterions) is described below withreference to blocks 4 c-4 e and 4 h-4 j of FIG. 4.

At block 4 c, a verification of whether a TOF-count is equal to zero anda TOF-ratio is equal to 0% may be performed. In case of a positiveresult of said verification, the method may proceed to block 4 d. Incase of a negative result of said verification, the method may continueto block 4 h.

At block 4 h, a verification of whether TOF-ratio is greater than orequal to 80% may be performed. In case of a positive result of saidverification, the neuromuscular status may be changed toend-of-reversion status 100 h. In case of a negative result of saidverification, the method may continue to block 4 i. This block is thuscomparable to blocks 3 h and 2 f

At block 4 i, a verification of whether TOF-ratio is greater than orequal to 10% may be performed. In case of a positive result of saidverification, the neuromuscular status may be changed to reversionstatus 100 g. In case of a negative result of said verification, themethod may continue to block 4 j. This block is thus generallycomparable to block 3 i.

At block 4 j, a verification of whether TOF-count is greater than zeromay be performed. In case of a positive result of said verification, theneuromuscular status may be changed to moderate status 100 b. In case ofa negative result of said verification, the method may loop back toblock 4 a. This block is thus comparable to block 3 j.

At block 4 d, a counter of consecutive TOF stimulations with TOF-countequal to zero and TOF-ratio equal to 0% may be increased and,afterwards, the method may continue to block 4 e.

At block 4 e, the method may comprise verifying whether the counter ofconsecutive TOF stimulations with a TOF-count equal to zero and aTOF-ratio equal to 0% is equal to 3. In case of a positive result ofsaid verification, the method may continue to block 4 f. In case of anegative result of said verification, the method may loop back to block4 a.

The intense status 100 f may further have predefined a PTC stimulationcycle with a cycle periodicity of e.g. approximately 6 minutes. At block4 f, the method may comprise waiting for 12 seconds after TOFstimulation and then causing performance of the predefined PTCstimulation cycle along with derivation of corresponding PTC-countparameter.

The intense status 100 f may also have predefined a second criterion orsecond set of criterions for changing the neuromuscular status. Thissecond criterion (or second set of criterions) is described below withreference to block 4 g of FIG. 4.

At block 4 g, a verification of whether FTC-count is greater than orequal to 8 may be performed. In case of a positive result of saidverification, the neuromuscular status may be changed to deep status 100e. In case of a negative result of said verification, the method mayloop back to block 4 a.

FIG. 5 is a flow chart schematically illustrating automatic changes fromreversion status 100 g to other statuses in the same or in a similarmethod. Reversion status 100 g may be attributed to the patientdepending on a previous phase 5PREV.

This previous phase 5PREV may be, for example, the “intense phase” 100 fdescribed in relation to FIG. 4. Other possible transitions to reversionstatus 100 g may be described in other parts of the description.

The reversion status 100 g may have a predefined TOF stimulation cyclewith e.g. a cycle periodicity of e.g. 1 minute. At block 5 a, the methodmay therefore comprise waiting for 1 minute and then, proceeding toblock 5 b. At block 5 b, performance of the predefined TOF stimulationcycle may be caused along with derivation of corresponding TOF-count andTOF-ratio parameters.

The reversion status 100 g may also have predefined first criterion(s)for changing the neuromuscular status. This first criterion(s) isdescribed below with reference to blocks 5 c-5 f of FIG. 5.

At block 5 c, a verification of whether a TOF-count is less than 4 maybe performed. In case of a positive result of said verification, themethod may proceed to block 5 d. In case of a negative result of saidverification, the method may continue to block 5 f.

At block 5 d, a counter of consecutive TOF stimulations with TOF-countless than 4 may be increased and, afterwards, the method may continue toblock 5 e.

At block 5 e, the method may comprise verifying whether the counter ofconsecutive TOF stimulations with TOF-count less than 4 is equal to 2.In case of a positive result of said verification, the neuromuscularstatus may be changed to moderate status 100 b. In case of a negativeresult of said verification, the method may loop back to block 5 a.

At block 5 f, the method may comprise verifying whether a TOF-ratio isgreater than or equal to 80%. In case of a positive result of saidverification, the neuromuscular status may be changed toend-of-reversion status 100 h. Again, it may thus be considered that thepatient's muscles are not blocked anymore. In case of a negative resultof said verification, the method may loop back to block 5 a.

FIG. 6 is a flow chart schematically illustrating automatic changes fromend-of-reversion status 100 h to other statuses in the same or in asimilar method. End-of-reversion status 100 h may be attributed to thepatient depending on a previous phase 6PREV.

This previous phase 6PREV may be, for example, the “reversion phase” 100g described in relation to FIG. 5. Other possible transitions toend-of-reversion status 100 g may be described in other parts of thedescription.

The end-of-reversion status 100 h may have a predefined TOF stimulationcycle with a cycle periodicity of e.g. approximately 30 seconds. Atblock 6 a, the method may therefore comprise waiting for 30 seconds andproceeding to block 6 b. At block 6 b, performance of the predefined TOFstimulation cycle may be caused along with derivation of correspondingTOF-count and TOF-ratio parameters.

The end-of-reversion status 100 h may also have predefined firstcriterion(s) for changing the neuromuscular status. These firstcriterions are described below with reference to blocks 6 c-6 h of FIG.6.

At block 6 c, a verification of whether a TOF-count is less than 4 maybe performed. In case of a positive result of said verification, themethod may proceed to block 6 d. In case of a negative result of saidverification, the method may continue to block 6 f.

At block 6 d, a counter of consecutive TOF stimulations with TOF-countless than 4 may be increased and, afterwards, the method may continue toblock 6 e.

At block 6 e, the method may comprise verifying whether the counter ofconsecutive TOF stimulations with TOF-count less than 4 is equal to 2.In case of a positive result of said verification, the neuromuscularstatus may be changed to moderate status 100 b. In case of a negativeresult of said verification, the method may loop back to block 6 a.

At block 6 f, a verification of whether TOF-ratio is less than 60% maybe performed. In case of a positive result of said verification, theneuromuscular status may be changed to reversion status 100 g. In caseof a negative result of said verification, the method may continue toblock 6 g.

At block 6 g, a weighted score may be applied by using a weightedcounter that has been set to zero at the beginning of the“end-of-reversion phase” 100 h, i.e. prior to the first execution ofblock 6 a. This weighted counter may be increased by one ifTOF-ratio≥91% and TOF-ratio≤94%, or increased by two if TOF-ratio≥95%and TOF-ratio≤98%, or increased by three if TOF-ratio≥99%. Once theweighted counter has been updated, the method may continue to block 6 h.

At block 6 h, a verification of whether the weighted counter is greaterthan or equal to 5 may be performed. In case of a positive result ofsaid verification, the neuromuscular status may be changed to unblockedstatus 100 d. In case of a negative result of said verification, themethod may loop back to block 6 a. When unblocked status 100 d isattributed to the patient, the method may end its execution.

FIG. 7 is a flow chart schematically illustrating an initial phase 700 aand a calibration phase 700 b which may be employed prior to the methodsfor determining a neuromuscular blockade status as hereinbeforedescribed.

The initial phase (or sub-method) 700 a may start at block 7 a, whereinthe initial sub-method 700 a may comprise verifying whether a muscleresponse of reference has been determined for the patient. In case of apositive result of said verification, a transition to block 7 b may beperformed.

In case of a negative result of said verification, the calibration phase(or sub-method) 700 b may be started at block 7 d.

At block 7 b, performance of an initial TOF stimulation cycle may becaused along with determination of corresponding TOF-count parameter.

At block 7 c, a verification of whether TOF-count is less than 4 may becarried out. In case of a positive result of said verification, moderatestatus 100 b may be initially attributed to the patient and, therefore,a sub-method identical or similar to the one illustrated by FIG. 2 maybe started. In case of a negative result of said verification, inductionstatus 100 a may be attributed to the patient and, therefore, asub-method identical or similar to the one illustrated by FIG. 1 may bestarted.

The calibration sub-method 700 b may have predefined a TOF stimulationcycle with a cycle periodicity of 12 seconds. At block 7 d, thecalibration sub-method 700 b may therefore comprise waiting for 12seconds and then, once elapsed said 12 seconds, proceeding to block 7 e.

At block 7 e, performance of the predefined TOF stimulation cycle may becaused along with derivation of corresponding TOF-count parameter.

At block 7 f, the calibration sub-method 700 b may comprise verifyingwhether a muscle response of reference has been determined for thepatient. In case of a positive result of said verification, thecalibration sub-method 700 b may continue to block 7 i. In case of anegative result of said verification, the calibration sub-method 700 bmay proceed to block 7 g.

At block 7 g, a counter of performed TOF stimulations may be increasedand, afterwards, the calibration sub-method 700 b may continue to block7 h.

At block 7 h, a verification of whether the counter of performed TOFstimulations is equal to 4 may be carried out. In case of a positiveresult of said verification, the calibration sub-method 700 b maycontinue to block 7 i. In case of a negative result of saidverification, the calibration sub-method 700 b may loop back to block 7d.

At block 7 i, a verification of whether TOF-count is less than 4 may beperformed. In case of a positive result of said verification, moderatestatus 100 b may be attributed to the patient and, therefore, asub-method identical or similar to the one illustrated by FIG. 2 may bestarted. In case of a negative result of said verification, inductionstatus 100 a may be attributed to the patient and, therefore, asub-method identical or similar to the one illustrated by FIG. 1 may bestarted.

The muscle response of reference may be determined either manually (i.e.outside the automatic initial and calibration sub-methods 700 a, 700 b)or automatically (i.e. by the calibration sub-method 700 b).

The muscle response of reference may be determined manually by causingperformance of a TOF stimulation cycle and subsequently deriving themuscle response of reference from the performed TOF stimulation.

FIG. 7 schematically shows that if the muscle response of reference hasnot been determined before, it may be automatically determined by thecalibration sub-method 700 b based on causing performance of up to 4 TOFstimulations with a periodicity of 12 seconds.

The muscle response of reference may be required to be greater than aminimum amplitude and to have a TOF-count parameter equal to 4. If thiswere not the case, the patient would be relaxed (i.e. affected by musclerelaxant(s)) and the muscle response of reference would be useless.

Determining the muscle response (either manually or automatically) mayfurther comprise determining an optimum stimulation (TOF) current forthe patient.

In clinical/surgical practice, the use of new drugs, such as e.g.Sugammadex, allowing a faster reversion of neuromuscular blockade isgrowing increasingly. These new drugs typically also facilitate the useof intense blockades if required.

FIGS. 1-7 illustrate sub-methods of methods for determining aneuromuscular blockade status a patient assuming that standard drugs arebeing used for causing either neuromuscular blockade or reversion of theneuromuscular blockade. The expression “standard drugs” is used hereinto indicate drugs that are currently normally used, i.e. drugs which arenot of the type described above i.e. for “faster reversion”.

FIG. 8 is a flow chart schematically illustrating a sub-method of amethod according to another example assuming that a “faster reversion”drug has been delivered to the patient.

This sub-method may be triggered when previous conditions 8PREV arefulfilled. A previous condition may comprise e.g. activation of anindicator representing that a “faster reversion” drug is being used.This activation may be provided by e.g. an anaesthesiologist (or similarprofile) through suitable means for data entry. If this indicator isactivated, the method may trigger this “faster reversion” sub-methodfrom e.g. deep status 100 e (FIG. 3) or intense status 100 f (FIG. 4)depending on respective first and/or second criterion(s) for changingthe neuromuscular blockade status.

This “faster reversion” sub-method may have predefined a TOF stimulationcycle with a cycle periodicity of 30 seconds. At block 8 a, thesub-method may therefore comprise waiting for 30 seconds and then, onceelapsed said 30 seconds, proceeding to block 8 b. At block 8 b,performance of the predefined TOF stimulation cycle may be caused alongwith derivation of corresponding TOF-count and TOF-ratio parameters.

At block 8 c, a counter of performed TOF stimulations may be increasedand, afterwards, the sub-method may continue to block 8 d.

At block 8 d, the sub-method may comprise verifying whether the counterof performed TOF stimulations is equal to 4. In case of a positiveresult of said verification, the sub-method may proceed to block 8 e. Incase of a negative result of said verification, the method may loop backto block 8 a.

At block 8 e, a verification of whether TOF-count is equal to zero andTOF-ratio is equal to 0% may be performed. In case of a positive resultof said verification, the sub-method may return to a standard method STD(assuming that a standard drug is being used). In case of a negativeresult of said verification, the method may continue to block 8 f.

At block 8 f, a verification of whether TOF-ratio is greater than orequal to 80% may be performed. In case of a positive result of saidverification, the neuromuscular status may be changed toend-of-reversion status 100 h. In case of a negative result of saidverification, the method may continue to block 8 g.

At block 8 g, a verification of whether TOF-ratio is greater than orequal to 7% may be performed. In case of a positive result of saidverification, the neuromuscular status may be changed to reversionstatus 100 g. In case of a negative result of said verification, themethod may continue to block 8 h.

At block 8 h, a verification of whether TOF-count is greater than zeromay be performed. In case of a positive result of said verification, theneuromuscular status may be changed to moderate status 100 b. In case ofa negative result of said verification, the method may return to thestandard method STD.

In relation to monitoring of partial neuromuscular blockade (see FIG. 1and descriptions about block 1 e), some particularities may be presentin examples of the method for carrying out said special monitoring ofpartial neuromuscular blockade.

For example, moderate status 100 b may have its first criterion or firstset of criterions adapted to store the minimum TOF-ratio measured and totransition to other statuses according to particular rules formonitoring partial neuromuscular blockade.

For example, a particular rule for partial neuromuscular blockade maycomprise transitioning to reversion status when TOF-ratio is greaterthan or equal to 50%, or when TOF-ratio is greater than or equal to theresult of adding the (stored) minimum TOF-ratio and 25%.

A further particular rule for partial neuromuscular blockade maycomprise transitioning from reversion status to moderate status whenfour consecutive TOF stimulations produce TOF-ratio less than 30%.

A still further particular rule for partial neuromuscular blockade maycomprise transitioning from end-of-reversion status to moderate statuswhen four consecutive TOF stimulations produce TOF-ratio less than 30%.

FIG. 9 schematically shows a pressure pulse 9 a due to a patient'sheartbeat and some parameters related to said pulse 9 a. The pressurepulse 9 a may have been obtained through a pressure cuff applied arounda patient's limb (e.g. arm). In particular, this pressure pulse 9 a mayrepresent how pressure varies over time inside the cuff as a result ofpatient's heartbeat.

The heartbeat pulse 9 a may have a start point 9 f, an upward slope 9 r,a peak 9 g, a downward slope 9 s, and an end 9 q. FIG. 9 illustratesthat a heartbeat pulse 9 a may have an amplitude 9 b, which may bedefined as the pressure variation in the heartbeat pulse 9 a between thepressure at start point 9 f and the peak 9 g.

The start 9 f of the heartbeat pulse 9 a may be defined as the point atwhich the heartbeat pulse 9 a substantially starts to rise from apressure variation substantially equal to zero. In other words, thestart 9 f of the heartbeat pulse 9 a may be defined as the point atwhich the upward slope 9 r of the heartbeat pulse 9 a substantiallystarts.

The end 9 q of the heartbeat pulse 9 a may be defined as the point atwhich the heartbeat pulse 9 a substantially ends to drop to a pressurevariation substantially equal to zero, i.e. the point at which thedownward slope 9 s of the heartbeat pulse 9 a substantially ends.

FIG. 9 further shows that a heartbeat pulse 9 a may also have associatedwith it a rising time 9 c, a maximum derivative 9 e, and a time of themaximum derivative 9 d. The rising time 9 c may be defined as the timeelapsed between the start 9 f and the peak 9 g of the heartbeat pulse 9a.

The maximum derivative 9 e may be defined as the maximum inclination ofa tangent line to the heartbeat pulse 9 a at any point of the upwardslope 9 r. The time of the maximum derivative 9 d may be defined as thetime elapsed between the start 9 f of the pulse 9 a and the point of themaximum derivative 9 e.

FIG. 10 schematically shows a muscle response pulse 10 h induced by anelectro stimulation pulse 10 m, and some parameters related to saidpulse 10 h. The muscle response pulse 10 h may have been obtainedthrough a pressure cuff applied around a patient's limb (e.g. arm). Inparticular, this muscle response pulse 10 h represents how pressurevaries over time inside the cuff as a muscle reaction to the electrostimulation pulse 10 m.

Similarly to the heartbeat pulse 9 a (of FIG. 9), the muscle responsepulse 10 h (of FIG. 10) may be defined or described by an amplitude 10 l(i.e. difference between pressure at starting point 10 j and peak 10 i),an upward slope 10 u, the peak 10 i, a downward slope 10 v, an end point10 t, a rising time 10 o, a maximum derivative 10 k, and time until themaximum derivative 10 p.

FIG. 10 shows a further parameter which is specific for this type ofpulses 10 h and may be called herein “stimulation-response” time 10 n.This stimulation-response time 10 n may be defined as the time elapsedbetween the electro stimulation pulse 10 m that induces the muscleresponse pulse 10 h and the start 10 j of the muscle response pulse 10 hitself.

FIGS. 11 and 12 schematically show respective views of a measured muscleresponse pulse 10 h induced by an electro stimulation pulse 10 m, and aheartbeat pulse 9 a interfering with the muscle response pulse 10 h.Both pulses 10 h, 9 a may have been obtained through a pressure cuff asexplained in other parts of the description.

FIG. 12 further shows an adjusted muscle response pulse 10 h′ which mayresult from performing a method for determining an “adjusted” or“filtered” muscle response 10 h′. The term “filtered” or “adjusted” isused herein to indicate that the measured muscle response 10 h isfiltered or adjusted (by the method) in such a way that interferencesdue to heartbeat(s) 9 a are at least partially eliminated resulting inthe adjusted muscle response pulse 10 h′.

FIG. 12 also shows an error 12 a in the amplitude of the measured muscleresponse pulse 10 h due to its coupling with the heartbeat pulse 9 a.This error 12 a may be at least partially eliminated by performing amuscle-response correction method, which may produce the adjusted muscleresponse 10 h′ without at least part of said error 12 a. Details aboutexamples of correction methods are provided in other parts of thedescription.

FIG. 13 schematically shows a sequence of heartbeat pulses 9 a, 13 a anda muscle response 13 f-13 i to a TOF stimulation 13 b-13 e. Both theheartbeat pulses 9 a, 13 a and the muscle response pulses 13 f-13 i mayhave been obtained through a pressure cuff as explained in other partsof the description.

FIG. 13 shows that muscle response pulses 13 f-13 i are induced by TOFstimulation pulses 13 b-13 e respectively. This Figure also shows thatsome heartbeat pulses 9 a occurring before the electro-stimulation donot cause any interference in muscle response pulses 13 f-13 i. However,other heartbeat pulses 13 a occurring substantially at the same time asthe electro-stimulation may interfere in muscle response pulses 13 f-13i.

FIG. 14 is a flow chart schematically illustrating a method ofdetermining a muscle response to an electro-stimulation in a patient,according to examples. For the sake of understanding, reference signs ofFIGS. 9 to 13 may be used in following descriptions about FIG. 14.

At block 14 a, the end 9 q of a heartbeat 9 a of the patient may bedetermined.

At block 14 b, a first electro-stimulation pulse 13 b may be generatedand, subsequently, one or more further electro-stimulation pulses 13c-13 e. The first electro-stimulation pulse 13 b may be generatedsubstantially at the end 9 q of the heartbeat 9 a.

At block 14 c, the muscle response may be determined in the form of apressure wave representing how pressure varies over time in a pressurecuff as a muscle reaction to the electro-stimulation. The pressure wavemay comprise first and further pressure pulses 13 f-13 i caused by thefirst and further electro-stimulation pulses 13 b-13 e respectively.

An aspect of causing generation of the first electro-stimulation pulse13 b substantially at the end 9 q of the heartbeat 9 a may be that thefirst pressure pulse 13 f may be substantially free of interference(s)with patient's heartbeat. This may thus permit taking the first pressurepulse 13 f (induced by first electro-stimulation pulse 13 b) as a model(or reference) for adjusting the further pressure pulses 13 g-13 i(provoked by further electro-stimulation pulses 13 c-13 e).

At block 14 d, a first characteristic indicative of the shape of theupward slope 10 u of the first pressure pulse 13 f may be determined.

At block 14 e, the first characteristic may be determined for each ofthe further pressure pulses 13 g-13 i.

At block 14 f, the method may comprise determining, for each of thefurther pressure pulses 13 g-13 i, a deviation between the firstcharacteristic of the further pressure pulse 13 g-13 i and the firstcharacteristic of the first pressure pulse 13 f.

At block 14 g, a verification of whether the deviation exceeds adeviation threshold may be performed. In case of a positive result ofsaid verification, a transition to block 14 h may be carried out. Incase of a negative result of said verification, a progression to block14 i may be performed. The deviation threshold may be in a range of10%-20%, preferably equal to 15%.

At block 14 h, each further pressure pulse 13 g-13 i may be adjustedbased on either a first assumption or a second assumption.

The first assumption may presume that the time 10 o until peak 10 i ofthe further pressure pulse 13 g-13 i is measured correctly (i.e. notsignificantly influenced by a coinciding heart pulse) and that the shapeof its upward slope 10 u can be described by the first characteristic ofthe first pressure pulse 13 f.

The second assumption may presume that the time 10 o until peak 10 i ofthe further pressure pulse 13 g-13 i is measured correctly and that theshape of its upward slope 10 u can be described by substantiallysubtracting a heartbeat pulse of reference 9 a from the measured furtherpressure pulse 13 g-13 i. In this case, there is an implicit assumptionthat the pressure pulse caused by heartbeat and the pressure pulsecaused by electro-stimulation are substantially simultaneous.

At block 14 i, each further pressure pulse 13 g-13 i may be adjustedbased on that the time 10 o until peak 10 i of the further pressurepulse 13 g-13 i is measured correctly and that the shape of its upwardslope 10 u can be described by the first characteristic of the firstpressure pulse 13 f.

The first characteristic of the pressure pulses 13 f-13 i may bedetermined, at blocks 14 d and 14 e, depending on the amplitude 10 l ofthe pressure pulse 13 f-13 i and the maximum derivative 10 k of theupward slope 10 u of the pressure pulse 13 f-13 i.

In particular, the first characteristic of the pressure pulse 13 f-13 imay be determined, at blocks 14 d and 14 e, based on the followingformula:

${C({pulse})} = \frac{A({pulse})}{d_{\max}({pulse})}$

wherein: C(pulse) is the first characteristic of the pressure pulse 13f-13 i, A(pulse) is the amplitude 10 l of the pressure pulse 13 f-13 i,and d _(max) (pulse) is the maximum derivative 10 k of the upward slope10 u of the pressure pulse 13 f-13 i.

The result of dividing the amplitude 10 l by the maximum derivative 10 kof the pulse 13 f-13 i conceptually represents the time until peak ifthe pressure pulse had a slope equal to the maximum derivative. Hence,the calculated first characteristic may be considered as a parameterrepresentative of the shape of the corresponding pulse 13 f-13 i.Alternatively, other parameters and/or other mathematical relationsbetween them could be considered for this aim.

Adjusting the further pressure pulse 13 g-13 i may comprise, at block 14i, adjusting the amplitude 10 l of the further pressure pulse 13 g-13 ibased on the following formula:A _(adjusted)(further_pulse)=C(first_pulse)×d _(max)(further_pulse)wherein: A_(adjusted)(further_pulse) is the adjusted amplitude of thefurther pressure pulse 13 g-13 i, C(first_pulse) is the firstcharacteristic of the first pressure pulse 13 f, andd_(max)(further_pulse) is the maximum derivative 10 k of the upwardslope 10 u of the further pressure pulse 13 g-13 i.

The result of multiplying the maximum derivative 10 k of the furtherpressure pulse 13 g-13 i by the result of dividing the amplitude 10 l bythe maximum derivative 10 k of the first pressure pulse 13 fconceptually represents that the time until peak of a further pulse hasbeen measured correctly (because the pressure variation of a pulsecaused by a heartbeat is much smaller than the pressure variation causedby electro-stimulation), but that the amplitude was influenced by thepresence of the heartbeat.

FIG. 15 is a flow chart illustrating an implementation of the block 14 hof FIG. 14, according to some examples.

At block 15 c, a first adjusted amplitude of the further pressure pulse13 g-13 i may be determined based on the first assumption. This firstadjusted amplitude may be calculated depending on the firstcharacteristic of the further pressure pulse 13 g-13 i in the same orsimilar way as done at block 14 i. Taking this into account, in someexamples, the result of blocks 14 i and 15 a may be the same.

At block 15 a, a second characteristic of the shape of the upward slope9 r of the heartbeat pulse of reference 9 a may be determined.

This second characteristic may be calculated depending on the amplitude9 b of the heartbeat pulse of reference 9 a and a time 9 c until peak 9g of the heartbeat pulse of reference 9 a. For example, this secondcharacteristic may be determined based on the following formula:

${C\left( {{hb\_}{pulse}} \right)} = \frac{A({hb\_ pulse})}{t_{S}({hb\_ pulse})}$wherein: C(hb_pulse) is the second characteristic of the heartbeat pulseof reference 9 a, A(hb_pulse) is the amplitude 9 b of the heartbeatpulse of reference 9 a, and t_(S)(hb_pulse) is the time 9 c until peak 9g of the heartbeat pulse of reference 9 a.

The above formula for determining the second characteristic conceptuallyrepresents an average inclination of the upward slope 9 r of theheartbeat pulse of reference 9 a. Therefore, this second characteristicmay be considered as an indicator representing the shape of theheartbeat pulse of reference 9 a, which may be useful for adjusting thefurther pressure pulses 13 g-13 i. Alternatively, other parametersand/or other mathematical relations between them could be considered forthis aim.

At block 15 b, a second adjusted amplitude of the further pressure pulse13 g-13 i may be determined based on the second characteristic(calculated at block 15 a) of the shape of the upward slope 9 r of theheartbeat pulse of reference 9 a. This second adjusted amplitude of thefurther pressure pulse 13 g-13 i may be determined further depending onthe amplitude 10 l of the further pressure pulse 13 g-13 i and the time10 o until peak 10 i of the further pressure pulse 13 g-13 i.

In particular, the second adjusted amplitude of the further pressurepulse 13 g-13 i may be determined, at block 15 b, based on the followingformula:A _(adjusted)(further_pulse)=A(further_pulse)−t_(S)(further_pulse)×C(hb_pulse)wherein: A_(adjusted)(further_pulse) is the second adjusted amplitude ofthe further pressure pulse 13 g-13 i, A(further_pulse) is the amplitude10 l of the further pressure pulse 13 g-13 i, t_(S)(further_pulse) isthe time 10 o until peak 10 i of the further pressure pulse 13 g-13 i,and C(hb_pulse) is the second characteristic of the heartbeat pulse ofreference 9 a.

The above formula for obtaining the second adjusted amplitude is basedon the basic assumption that a heartbeat pulse of the patientsubstantially completely coincides (i.e. interferes) with the furtherpressure pulse 13 g-13 i.

For this reason, the second adjusted amplitude can be obtained bysubtracting the result of multiplying the rising time 10 o of thefurther pressure pulse 13 g-13 i by the average inclination of theupward slope 9 r of the heartbeat pulse of reference 9 a from themeasured amplitude 10 l of the further pressure pulse 13 g-13 i. Thismay conceptually represent that the heartbeat pulse of reference 9 a issubtracted from the measured further pressure pulse 13 g-13 i.

At block 15 d, a verification may be performed of whether the firstadjusted amplitude is smaller than the second adjusted amplitude. Incase of a positive result of said verification, a transition to block 15e may be performed.

In case of a negative result of said verification, a transition to block15 f may be performed.

At block 15 e, the first adjusted amplitude may be selected as theresult of adjusting the further pressure pulse 13 g-13 i. At block 15 f,the second adjusted amplitude may be selected as the result of adjustingthe further pressure pulse 13 g-13 i. In other words, the smaller of thefirst and second adjusted amplitudes is selected as the result ofadjusting the further pressure pulse 13 g-13 i.

An aspect of selecting the smaller of the first and second adjustedamplitudes may be that an excessive correction of the further pressurepulse 13 g-13 i may be avoided. The second adjustment can generally bemore aggressive (i.e. of larger magnitude) than the first adjustment,but this selection of the smaller adjustment may be carried out as aprecautionary step for avoiding an excessive correction of the furtherpressure pulse 13 g-13 i.

The electro-stimulation caused at block 14 b may be anelectro-stimulation according to a Train of four (TOF) pattern based ongenerating a first electro-stimulation pulse 13 b and three furtherelectro-stimulation pulses 13 c-13 e. Taking this into account, themuscle response may be determined, at block 14 c, having a TOF-ratioparameter corresponding to a relation between the amplitude of one ofthe three further pressure pulses 13 g-13 i and the amplitude of thefirst pressure pulse 13 f.

The TOF-ratio parameter may be determined, at block 14 c, based on afirst verification of thatA(first_pulse)≥A(second_pulse)≥A(third_pulse)≥A(fourth_pulse), whereinA(first_pulse), A(second_pulse), A(third_pulse) and A(fourth_pulse) arethe adjusted amplitude of the first, second, third and fourth pressurepulses 13 f-13 i respectively. Physiologically speaking, it isinevitable that the muscle response to the four pulses of the TOFdecrease with each pulse.

In case of a positive result of said first verification, which mayindicate that the first, second, third and fourth pressure pulses 13f-13 i are not so influenced by heartbeats so as to be at odds with thebasic physiological truth mentioned before, the TOF-ratio parameter maybe calculated (as usual) as the percentage of the fourth pressure pulse13 i with respect to the first pressure pulse 13 f.

In case of a negative result of said first verification, the TOF-ratioparameter may be determined based on a second verification of thatA(first_pulse)≥A(second_pulse)≥A(third_pulse)<A(fourth_pulse). In caseof a positive result of said second verification, which may indicatethat only the first, second and third pressure pulses 13 f-13 h aresufficiently reliable, the TOF-ratio parameter may be determined basedon the following formula:

${TOF}_{RATIO} = \left( \frac{A({third\_ pulse})}{A({first\_ pulse})} \right)^{X}$wherein: TOF_(RATIO) is the TOF-ratio parameter, and X is a value usedto compensate that the TOF-ratio parameter is calculated depending onthe amplitude of the first and third pulses rather than the fourthpulse.

In case of a negative result of said second verification, the TOF-ratioparameter may be determined based on a third verification of thatA(first_pulse)≥A(second_pulse)<A(third_pulse)). In case of a positiveresult of said third verification, which may indicate that only thefirst and second pressure pulses 13 f, 13 g are sufficiently reliable,the TOF-ratio parameter may be determined based on the followingformula:

${TOF}_{RATIO} = \left( \frac{A({second\_ pulse})}{A({first\_ pulse})} \right)^{Y}$wherein Y is a value used to compensate that the TOF-ratio parameter iscalculated depending on the amplitude of the first and second pulsesrather than the third and fourth pulses.

An aspect of the previous manner of determining the TOF-ratio parametermay be that a relatively reliable value may be obtained for saidparameter even in the case of estimating that some of the pressurepulses 13 f-13 i are very unreliable. It is considered however that, inmost cases, the TOF-ratio parameter may be properly calculated from thefirst and fourth pressure pulses 13 f, 13 i.

FIGS. 16a-16e illustrates an electro-stimulation electrode according toa first example, and FIGS. 17a-17g illustrates an electro-stimulationelectrode according to a second example. The electro-stimulationelectrodes are adapted to be applied dryly (or are suitable for dryapplication i.e. without the need of applying any electricallyconductive gel under them) on a portion of skin, preferably a portion ofintact skin of a patient.

Both electro-stimulation electrodes comprise a support layer 161, anelectrically conductive medium 163, and a first conductive layer 164.

The support layer 161 may be made of an electrically insulating materialand its outer surface is aimed at coming into contact with the skin ofthe patient. In other words, the support layer 161 is arranged in such away that, in use, its outer surface contacts the patient's skin.

The support layer 161 is provided with at least one region provided withone or more holes 162 in the surface of contact with the patient.

The electrically conductive medium 163 is adhered to the inner surfaceof the support layer 161. This inner surface of the support layer 161 isthe opposite surface to the surface of contact with the skin of thepatient.

The electrically conductive medium 163 is arranged around the region 162provided with one or more holes, such that the electrically conductivemedium 163 completely or partially surrounds said region 162 in such away that the electrically conductive medium 163 does not overlap with orcover said region 162.

The first conductive layer 164 contacts the electrically conductivemedium 163 in such a way that the first conductive layer 164 at leastpartially covers or overlaps with the region with the at least one hole162.

With respect to the first example, the following particular features arenoted.

As can be seen in FIG. 16d , the electrically conductive medium 163 isarranged between the support layer 161 and the first conductive layer164. A second conductive layer 165 is arranged on the surface of contactwith the patient's skin, said second conductive layer 165 being incontact with the first conductive layer 164 through the one or moreholes 162.

As can be seen in FIGS. 16d and 16e , the second conductive layer 165has a convex top surface or a top surface provided with relief (orprotruding portions) at the level of the region with holes 162, so thatthe contact with the skin of the patient is enlarged and ensured.

In this example, an arrangement as the one illustrated in FIG. 16a ,i.e. with (micro) holes 162 in the support layer 161, is preferred, sothat vertical forces to be supported by the thin conductive layers 164,165 of the electrode are minimized.

This is because the possible orthogonal forces that may gravitate on theelectrode are supported by the remaining non-perforated part of theresistant support layer 161, and not by the thin and delicate conductivelayers 164, 165 themselves.

With respect to the second example, the following particular featuresare noted.

As can be seen in FIG. 17g , the first conductive layer 164 is arrangedbetween the electrically conductive medium 163 and the support layer161. In this case, a second conductive layer 165 is arranged between thefirst conductive layer 164 and the support layer 161, said second layercovering the hole 162.

A third layer 176 is arranged between the first conductive layer 164 andthe second conductive layer 165, the third layer 176 having an outlinesubstantially complementary to the outline of the hole 162 and beingarranged coincident therewith (or fitted therein).

In this second example, there is an inner covering layer 177 whoseoutline exceeds the outline of the first and second conductive layers164, 165.

The support layer 161 may be made of Nylon, paper or a nonwoven fabricand the electrode (when in use) comes into contact with the skin of thepatient through the small window 162 existing thereon. The layer 163 isthe terminal end of a conductive track through which electricity isconveyed to the electrode. Such a conductive track can be manufacturede.g. either by depositing an electrically conductive metallic fabric orby printing an electrically conductive ink on the inner surface of thesupport layer 161.

The layers 164, 165 and 176 give shape to the body of the Electrode, andcan be manufactured by printing an ink of conductive composite (e.g. aliquid silicone-based matrix doped with electrically conductiveparticles) or intrinsically conductive polymer (ICP).

The printing of the layer 164 should be enough for obtaining afunctional electrode. However, printing of the other two layers 165, 176is generally preferred.

The layer 176 has a main objective of levelling the front surface of thelayer 164, since said layer 164 has a slight cavity in its centre, whichis due to the step (or protruding region) of the layer 164 which isintroduced in the central hole of the layer 163.

The layer 165 has the single objective of acting as a closure (or cover)of the layer 176, thereby avoiding that said layer 176 could detach fromthe layer 164 and leave the electrode through the hole 162 existing inthe fabric that constitutes the layer 161.

As can be seen in FIGS. 16a and 17a , the electrically conductive medium163 completely surrounds the region of the support layer 161 providedwith one or more holes 162.

In both examples, the electrically conductive medium 163 may be e.g. aconductive track, a cable, a conductive metallic fabric or a printedconductive ink.

FIG. 18 shows a hybrid air-signal connector 18 a for a pressure cuff forelectro-stimulation 23 r (see FIG. 23), which is adapted forimplementing a connection with an air-signal tube 23 p (see FIG. 23) forthe conveyance (or introduction) of both pressurized air and electricalsignals.

The hybrid air-signal connector 18 a comprises a main body and twosubstantially L-shaped electrodes 18 d, 18 e. The main body has a base18 b from which a first tubular portion 18 c extends on a (outer) sideat its centre, the first tubular portion 18 c being suitable for thecoupling of the tube 23 p.

That is, the main body has a base 18 b with a first tubular portion 18 carranged on a first side (or outer side) 18 g of the base 18 b in such away that, in use, the first tubular portion 18 c is fitted into an airconduit of the tube 23 p.

The L-shaped connection electrodes 18 d, 18 e have external terminals 18h, 18 j for connection with external wires (i.e. external to thepressure cuff), and internal terminals 18 i, 18 k for connection withconductive tracks 24 q (see FIG. 24) internal to the cuff 23 r. FIG. 24schematically partially shows an inner side of the outer envelope (orinflatable bag) 23 o of the cuff 23 r, which may also be referred to asbase-fabric 23 o hereinafter.

The external terminals 18 h, 18 j extend from the base 18 bsubstantially parallel (and optionally substantially contiguously) tothe first tubular portion 18 c. The external terminals 18 h, 18 j aretherefore arranged in such a way that, in use, each external terminal 18h, 18 j contacts an electrically conductive wire of the air-signal tube23 p.

The internal terminals 18 i, 18 k may be embedded in the base 18 b withtheir ends 19 m, 19 n exposed on the outer side 18 g of the base 18 b.In other words, the internal terminals 18 i, 18 k may be embedded in thebase 18 b with an end portion 19 m, 19 n arranged on the outer face ofthe base 18 b in such a way that, in use, the end portions 19 m, 19 ncan contact an inner conductive track 24 q of the cuff 23 r when thehybrid air-signal connector 18 a is introduced into a connection bore ofthe cuff 23 r (see FIG. 24).

The hybrid air-signal connector 18 a comprises a cylindrical enclosure18 f for protecting the external terminals 18 h, 18 j and guiding thecoupling of the tube 23 p which serves to transmit air and electricalsignals. This cylindrical enclosure 18 f may be described as a secondtubular portion 18 f outwardly coaxially arranged with respect to thefirst tubular portion 18 c.

The cylindrical enclosure 18 f may also constitute a barrier avoidingthe intrusion of liquids and/or dust in the connection between the tube23 p and the connector 18 a.

The cylindrical enclosure (or second tubular portion) 18 f has a lowerheight (or length) than the first tubular portion 18 c. Once the tube 23p has been inserted into the cylindrical enclosure 18 f, the welding ofboth components ensures both protection against intrusions andmechanical resistance of the connection between the tube 23 p and theconnector 18 a.

As shown in the figures, the hybrid air-signal connector 18 a maypreferably be made up of only three single bodies: the main body and thetwo electrodes 18 d, 18 e. This configuration or structure can beobtained through injection on and around (i.e. overmolding) the metallicelectrodes 18 d, 18 e placed inside a thermoplastic injection mould.

Preferably, polyurethane is used as base material for the injection ofthe body of the connector 18 a, and copper as base material for thestamping and die-cutting of the metal electrodes 18 d, 18 e. As can beseen in e.g. FIG. 18, the external terminals 18 h, 18 j aresubstantially cylindrical (i.e. have a substantially circularcross-section), and the internal terminals 18 i, 18 k are substantiallyflat (i.e. have a flat shape).

In FIG. 19, the base 18 b can be seen comprising a central ring 191 for(providing) pneumatic air tightness (to the connector 18 a). The centralring 191 protrudes with respect to the rest of the base 18 b at a firstside (or outer side) 18 g of the base 18 b. When suitably coupled to thecuff 23 r, this ring 191 will come into contact with an inner side ofthe base-fabric 230 (or fabric constituting the envelope) of the cuff 23r.

This last feature provides a wide and uninterrupted (i.e. 360 degrees ofscope) contact surface through which pneumatic air tightness of theconnection between the connector 18 a and the cuff 23 r is ensured. Suchpneumatic air tightness will be definitely ensured by the subsequentwelding of the base-fabric 23 o against the central ring 191.

FIG. 20 is a bottom perspective view of the hybrid air-signal connector18 a showing that the base 18 b may comprise holes 20 s for accessing tothe ends (or end portions) 19 m, 19 n of the internal terminals 18 i, 18k from the bottom (or inner) side of the base 18 b.

FIG. 21 is a front cross-sectional view of the hybrid air-signalconnector 18 a, wherein previously described configuration features canbe seen from another point of view. The central ring 191 for pneumaticair tightness can be seen protruding with respect to the rest of thebase 18 b at a first side (or outer side) of the base 18 b. An internalterminal end portion 19 n can also be seen arranged on the first side(or outer side) of the base 18 b, in such a way that said end portion 19n is exposed.

In FIG. 22, the electrodes 18 d, 18 e are shown arranged asymmetricallyin order to ensure a proper polarity in the connection. As can be seenalso in FIG. 22, the base 18 b may have a substantially ellipticalshape.

FIG. 23 is a perspective view of a pressure cuff 23 r and a tube 23 pconnected to the cuff 23 r through the hybrid air-signal connector 18 a.

FIG. 24 illustrates that, upon insertion of the hybrid air-signalconnector 18 a into the opening of the cuff 23 r aimed at that purpose,the end portions 19 m, 19 n (not shown in FIG. 24) of the metalelectrodes 18 i, 18 k (inevitably) come into contact with thecorresponding conductive tracks 24 q. These tracks 24 q are printed onor adhered to an inner surface of the base-fabric 23 o of the cuff 23 r.

In any of the previous examples, the main body of the connector 18 a maybe made e.g. of polyurethane.

FIG. 25 is a perspective view of a hybrid air-signal connector,according to a further example, for connecting a pressure cuff forelectro-stimulation and an air-signal tube. FIG. 26 is a cross-sectionalview of said hybrid air-signal connector. This hybrid air-signalconnector is similar to the ones shown in previous Figures. Onedifference is that, in this particular case, the connector comprisesfirst and second connection electrodes 25 a, 25 b with flat shapeinstead of the L shape previously described in the context of otherexamples.

The first flat electrode 25 a is shown embedded in a base 18 b of thehybrid air-signal connector and having an external terminal 26 b and aninternal terminal 26 a. The second flat electrode 25 b is also shownembedded in the base 18 b of the hybrid air-signal connector and havingan external terminal 26 c and an internal terminal 26 d.

Each of the external terminals 26 b, 26 c is shown arranged on the base18 b in such a way that, in use, the external terminal 26 b, 26 ccontacts an end of an electrically conductive cable of the air-signaltube when a corresponding tubular portion 18 c (of the connector) isfitted into an air conduit of the air-signal tube. Said tubular portion18 c is not shown in FIG. 25 in order to not obscure the depiction ofthe electrodes 25 a, 25 b.

Each of the internal terminals 26 a, 26 d is shown arranged on the base18 b in such a way that, in use, the internal terminal contacts an innerconductive track 24 q of the pressure cuff 23 r when the hybridair-signal connector is introduced into a connection bore of thepressure cuff.

An advantageous aspect of such a hybrid air-signal connector with flatelectrodes 25 a, 25 b may be that said connector yields a substantiallylower risk of failure during the splicing (or coupling) of the externalterminals 26 b, 26 c to corresponding electrically conductive cables ofthe air-signal tube. This is a consequence of the substantially largercontact surface offered by said external terminals 26 b, 26 c.

Said splicing may simply be a collateral effect of the coupling of theair-signal tube 23 p with the air-signal connector 18 a, which iscarried out by fitting the first tubular portion 18 c of the air-signalconnector into the air conduit of the hybrid air-signal tube. In thissplicing operation, the increased contact surface offered by theflat-shaped external terminals 26 b, 26 c may effectively relieve theoperator from e.g. the requirement of ensuring a substantially perfectcoaxial alignment between each of the external terminals of theconnector and corresponding electrically conductive cable of theair-signal tube.

Most of the principles and features previously commented with respect tohybrid air-signal connectors with L-shaped electrodes may be compatiblewith this last hybrid air-signal connector with flat electrodes. Any ofsaid compatible principles and features may thus be equally or similarlyapplied to obtain diverse configurations of hybrid air-signal connectorswith flat electrodes.

FIGS. 27a-27d have been described before.

FIGS. 28a-c and 29a-b schematically illustrate views similar to the oneshown in FIG. 27b but with a new examples of configurations ofelectrodes arranged across the width W of the pressure cuff 270.

FIG. 28a schematically illustrates a view similar to the one shown inFIG. 27b but with a new example of configuration of electrodes. Inparticular, an active electrode 284 a (or cathode or negative lead,through which current is supplied) and a passive electrode 283 a (oranode or positive lead, through which current is collected) are shownarranged on a pressure cuff region 282 a in such a way that, in use,both electrodes 283 a, 284 a are placed on the path 281 a of theperipheral motor nerve to be electro-stimulated. However, the passiveelectrode 283 a has a contact surface larger in size than the contactsurface of the active electrode 284 a.

This configuration may permit minimizing or avoiding the risk ofappearance of the “Anodal Block of Conduction” phenomenon, irrespectiveof whether the cuff is applied to the left or right arm (or leg) of thepatient.

When the active electrode 284 a is in a distal position and the passiveelectrode 283 a is in a proximal position, the “Anodal Block ofConduction” phenomenon cannot occur according to Pflüger's Law.

When the active electrode 284 a is in a proximal position and thepassive electrode 283 a is in a distal position, the larger size of thepassive electrode 283 a may induce a relatively low hyperpolarizationlevel in the underlying peripheral motor nerve's outer membrane. Thismay minimize or eliminate the risk of appearance of the “Anodal Block ofConduction” phenomenon, as argued in other parts of the description. Thesame principle applies to configurations shown in other Figures.

This configuration may also improve the electrical protection of thepatient's heart, since the larger size of the passive electrode 283 aconstitutes an effective and preferential exit for theelectro-stimulation current transmitted by the active electrode 284 a,as argued in other parts of the description. This principle will beequally used with reference to other Figures.

FIG. 28b schematically illustrates a view similar to the one shown inFIG. 28a but with another example of configuration of electrodes. Anactive electrode 284 b and a passive electrode 283 b are shown arrangedon a pressure cuff region 282 b in such a way that, in use, only theactive electrode 284 b is placed on the path 281 b of the peripheralmotor nerve to be electro-stimulated.

This arrangement of electrodes may permit avoiding the risk ofappearance of the “Anodal Block of Conduction” phenomenon, irrespectiveof whether the cuff is applied to the left or right arm (or leg) of thepatient.

When the cuff is applied to the right arm, the passive electrode 283 bis placed outside the path 281 b of the nerve to be stimulated. When thecuff is applied to the left arm, the passive electrode 283 b is equallyplaced outside the nerve path 281 b.

FIG. 28c schematically illustrates a view similar to the ones shown inFIGS. 28a and 28b but with another example of configuration ofelectrodes. An active electrode 284 c and a passive electrode 283 c areshown arranged on a pressure cuff region 282 c in such a way that, inuse, the active electrode 284 c is placed on the path 281 c of theperipheral motor nerve to be electro-stimulated and the passiveelectrode 283 c completely surrounds the active electrode 284 c in acoaxial manner with respect to a central axis 285 c. The passiveelectrode 283 c is larger in size than the active electrode 284 c.

With this configuration, a portion of the passive electrode 283 c willalways be laid out in a further distal position on the path 281 c of theperipheral motor nerve, irrespective of whether the cuff is applied onthe right or left limb of the patient. However, the relative larger sizeof the passive electrode 283 c may minimize the risk of appearance ofthe “Anodal Block of Conduction” phenomenon, according to the principledescribed with respect to FIG. 28a , in which case a reliable muscleresponse will always occur.

This configuration may also improve the electrical protection of thepatient's heart according to the principle described with respect toFIG. 28 a.

FIG. 29a schematically illustrates a view similar to the ones shown inFIGS. 28a-28c but with another example of a configuration of electrodes.An active electrode 294 a is shown to be arranged, in use, on theperipheral motor nerve path 291 a. A passive electrode 293 a is shownpartially surrounding the active electrode 294 a and formed as twoannular segments 296 a, 297 a.

A first of the annular segments 296 a has a first end 2910 a and asecond end 298 a, and a second of the annular segments 297 a has a firstend 2911 a and a second end 299 a. The first ends 2910 a, 2911 a areshown facing each other with a first gap in between and the second ends298 a, 299 a are shown facing each other with a second gap in between,such that, in use, the passive electrode 293 a is not directly arrangedon/over the nerve path 291 a.

This arrangement of electrodes may permit avoiding the risk ofappearance of the “Anodal Block of Conduction” phenomenon, since thepassive electrode 293 a is placed, in use, outside the nerve path 291 a,irrespective of whether the cuff is applied to the right or left arm (orleg) of the patient. Hence, a reliable muscle response will always occurin this case.

This configuration may also improve the electrical protection of thepatient's heart according to the principle described with respect toFIG. 28 a.

FIG. 29b schematically illustrates a view similar to the ones shown inFIGS. 28a-29a but with another example of configuration of electrodes.An active electrode 294 b is shown to be arranged, in use, on the nervepath 291 b. A passive electrode 293 b is shown partially surrounding theactive electrode 294 b and substantially C-shaped. The passive electrodeis shown having a first end 298 b and a second end 299 b facing eachother with a gap in between.

Such an arrangement of electrodes may permit minimizing or avoiding therisk of appearance of the “Anodal Block of Conduction” phenomenon, inwhich case a reliable muscle response will always occur.

The cuff may be applied on a patient's limb in such a way that thefurthest distal stretch of the nerve path 291 b substantially lies belowthe gap of the passive electrode 293 b. In this case, the passiveelectrode 293 b would not induce any hyperpolarisation on the outermembrane of the nerve. Hence, the risk of appearance of the “AnodalBlock of Conduction” phenomenon is eliminated.

Alternatively, the cuff can be applied on a patient's limb in such a waythat the furthest distal stretch of the nerve path 291 b falls below aportion of the passive electrode 293 b. In this case, the relativelarger size of the passive electrode 293 b may still minimize the riskof appearance of the “Anodal Block of Conduction” phenomenon, accordingto the principle described with respect to FIG. 2 a.

This configuration may also improve the electrical protection of thepatient's heart according to the principle described with respect toFIG. 28 a.

FIG. 30a schematically illustrates a sectional view of a portion 306 ofa laminated base material suitable for constructing electro-stimulationcircuits according to an example. This particular laminated basematerial 306 is shown formed as a multilayer film having a first layer302 of thermoplastic polymer doped with electrically conductiveparticles 307 and a second layer 303 of electrically conductivematerial. The first layer 302 and the second layer 303 may be attachedto each other with a heated lamination process as shown in FIG. 30 c.

FIG. 30b schematically illustrates a sectional view of a portion 306′ ofanother laminated base material suitable for constructingelectro-stimulation circuits according to another example. In this case,the laminated base material 306′ is shown formed as a multilayer filmhaving a first layer 302 of thermoplastic polymer doped withelectrically conductive particles 307, a second layer 303 ofelectrically conductive material, and a third layer 304 of thermoplasticpolymer that may also be doped with electrically conductive particles307.

These three layers 302-304 may be attached together in such a way thatthe second layer 303 is sandwiched between the first layer 302 and thethird layer 304. This attachment may be implemented through a heatedlamination process as the one illustrated in FIG. 30 c.

FIG. 30c schematically illustrates a process of fabricating a laminatedbase material similar to the ones shown in FIGS. 30a and 30b . Thisprocess may be a heated lamination process based on introducing twocorresponding sheets 302, 303 (for obtaining the structure of FIG. 30a )or three corresponding sheets 302-304 (for obtaining the structure ofFIG. 30b ) into a lamination apparatus.

This lamination apparatus may comprise at least two rollers 300, 301configured to rotate while pressing the input sheets 302, 303 or 302-304in such a way that a desired multilayer film 305 is generated. Suitableheating means may provide a proper heating at the pressure regionbetween the rollers 300, 301 in such a way that a relatively strongattachment between the layers or sheets 302, 303 or 302-304 may beimplemented.

An aspect of using this heated lamination process is that a relativelycompact multilayer film 305 can be obtained without the need of usingadhesives or similar substances. Since this multilayer film 305 isintended for constructing electro-stimulation circuits to be applied onthe skin of a human being, the absence of such adhesives (or similarsubstances) may avoid causing undesired alterations, such as e.g.irritation, of the skin.

Another aspect of using this heated lamination process is that it maymake the fabrication of the multilayer film 305 easier and cheaper incomparison with other types of manufacturing processes. For example, thelayer-by-layer deposition of thin films, which is typically used e.g. inthe Printed Electronics Industry and/or the Phase-Vapour Depositiontechnology, may require several intermediate steps.

The effective deposition of each layer included in the multilayer filmmay comprise e.g. the printing/deposition step itself, the subsequentcuring step (often, this step is compulsorily performed off-line of themain manufacturing printing line), a subsequent registry step of themultilayer stack already deposited with the silk-screen printingapparatus when back into the printing line, etc.

Nevertheless, the proposed heated lamination process may be just asingle-step and single-machine process which, as a result, can make themanufacturing process of the base material 305 more easily scalable tomass production.

A further aspect of using this heated lamination process is that arelatively thin and efficient multilayer film 305 for constructingelectro-stimulation circuit(s) may be obtained.

Once generated, a laminated base material such as the ones shown inFIGS. 30a and 30b may be properly cut for obtaining different examplesof electro-stimulation circuits, such as e.g. the ones shown in FIGS.31b and 32. These electro-stimulation circuits may comprise an electrodeportion and a track portion integrally formed as a single multilayerfilm having a laminated structure such as the ones described withreference to FIGS. 30a and 30 b.

The electrode portion may be configured to be arranged on a skin regionof a patient and to either transmit or collect an electrical currentto/from a region of a patient which is at least partially on a nerve ofthe patient for electro-stimulating a peripheral motor nerve. The trackportion may be configured to conduct the electrical current to/from theelectrode portion.

In a laminated base material such as the ones shown in FIGS. 30a and 30b, the thermoplastic polymer may comprise Thermoplastic polyurethane(TPU), and/or Polyvinyl chloride (PVC), and/or any other thermoplasticpolymer suitable for the intended aim(s). Furthermore, in some examples,the electrically conductive particles 307 may be graphite particles orany other type of electrically conductive particles suitable for theintended aim(s). The thermoplastic polymer film may be obtained byextruding pellets.

If the thermoplastic polymer and the electrically conductive particlesare combined under a suitable mixing ratio, a desired electricalconductivity of the layers 302, 304 may be achieved while keeping goodwelding capabilities. An aspect of the proposed electro-stimulationcircuits is thus that they may be easily welded to a region of the cuff,due to the presence of the thermoplastic polymer, in such a way thatskin friendly current transmissions may occur due to the presence of theelectrically conductive particles.

According to examples, the second layer may comprise an electricallyconductive fabric, which may be at least partially made of carbon fibreand/or may be at least partially made of metallic mesh. The layer madeof thermoplastic polymer doped with electrically conductive particlesmay still have a relatively low nominal value of electrical conductivitywhich may be not enough for the track portion to conduct electricityto/from the electrode portion efficiently.

The proposed second layer made of electrically conductive fabric mayprovide a good electrical conductivity for the track portion to conductelectricity to/from the electrode portion in an efficient manner. Hence,a circuit having an electrode portion and a track portion in the form ofsuch a multilayer single film is provided with suitable properties forboth the electrode portion and the track portion at the same time. Thismay reduce complexity and costs of fabrication of said circuits and itsapplication to the industrial manufacturing of electro-stimulationpressure cuffs like the one disclosed in U.S. Pat. No. 5,957,860A.

FIG. 31a schematically illustrates a pressure cuff 310 comprisingelectro-stimulation circuits according to examples. In particular, thispressure cuff 310 may be configured to be arranged around a limb of apatient and is shown comprising two electro-stimulation circuits. Afirst of the electro-stimulation circuits may comprise an electrodeportion 313 and a track portion (not shown), and a second of theelectro-stimulation circuits may comprise an electrode portion 314 and atrack portion (not shown).

Each of the two electro-stimulation circuits may be internally attachedto the pressure cuff 310 in such a way that, in use, a contact surfaceof the electrode portion 313, 314 of the electro-stimulation circuit isarranged on a region of the limb, which is at least partially on aperipheral motor nerve of the limb such that an electrical current canbe either transmitted or collected by the electrode portion 313, 314to/from said region of the limb for electro-stimulating the nerve.

The pressure cuff 310 is shown further comprising a fabric cover 315 anda hybrid tube 316 configured to conduct air and electricity between thecuff 310 and e.g. a monitor configured to operate the pressure cuff 310.The fabric cover 315 may comprise a hole for each of the electrodeportions 313, 314 of the electro-stimulation circuits in such a waythat, in use, a contact surface of the electrode portions 313, 314 arearranged on target regions of the patient for stimulating a peripheralmotor nerve.

FIG. 31b schematically illustrates an enlarged view of a region of apressure cuff similar to the one depicted in FIG. 31a from the point ofview 311 indicated in FIG. 31a . A first of the circuits may comprise anelectrode portion 319 and a track portion 318, and a second of thecircuits may comprise an electrode portion 3112 and a track portion3111.

The track portion 318 may connect the electrode portion 319 with acorresponding conductive wire of the hybrid tube 316. The track portion3111 may connect the electrode portion 3112 with a correspondingconductive wire of the hybrid tube 316. The hybrid tube 316 may connectthe cuff 310 with a monitor (not shown) for operating the cuff 310. Themonitor may have an electricity source (for electro-stimulation) whichcan thus be connected with the electrode portions 319, 3112 throughcorresponding conductive wires of the hybrid tube 316 and the trackportions 318, 3111 respectively.

The track portions 318, 3111 and the electrode portions 319, 3112 aredepicted with dashed lines to indicate that they are attached to aninternal side of the fabric cover 315 and, therefore, they are notvisible in the view provided by FIG. 31b . The fabric cover is shownhaving an opening 310 through which current transmissions between theelectrode portion 319 and the patient's skin can occur. The fabric coveris shown having another opening 3113 through which current transmissionsbetween the electrode portion 3112 and the patient's skin can occur.

FIG. 32 schematically illustrates a cross sectional view 323 of apressure cuff region similar to the one shown in FIG. 31b . This view323 has been taken according to a plane AA indicated in FIG. 31b . FIG.32 comprises a view 322 similar to the view of FIG. 31b and dashed linesof reference for better understanding of the cross sectional view 323.

The fabric cover 315 is shown formed as a multilayer fabric having anouter layer 320 made of e.g. nylon and an inner layer 321 made of e.g.thermoplastic polymer. The outer layer of nylon 320 may generallyattribute enough strength to the cuff 310 for supporting its normalmanipulation by medical operators.

The inner layer of thermoplastic polymer 321 may permit a relativelystrong attachment of the electro-stimulation circuits 318, 319, 3111,3112 to the cuff, and can contribute to making the inflatable bag of thepressure cuff leak-proof. Hence, a relatively compact and resistantpressure cuff may be obtained with the proposed multilayer fabric cover315.

The multilayer fabric cover 315 may be obtained with a heated laminationprocess similar to the one described for fabricating the multilayer basematerial of the electro-stimulation circuits. As commented with respectto the multilayer base material for the electro-stimulation circuits,the use of a heated lamination process for fabricating the multilayerfabric cover 315 may be that adhesives or similar substances may not berequired, such that a skin friendly multilayer fabric cover 315 may beobtained.

Another aspect of using this heated lamination process for manufacturingthe multilayer fabric cover 315 may be that the fabrication process mayresult easier and cheaper in comparison with other types of processes,such as e.g. a multi-material thin-film hot co-extrusion process. Afurther aspect of using this heated lamination process may be that arelatively thin, leak-tight, efficient, and cost-effective multilayerfabric cover 315 may be obtained.

In the particular case of FIG. 32, the electro-stimulation circuits 318,319, 3111, 3112 are shown formed as a single multilayer film with threelayers 302-304 similar to the layered structure of FIG. 30b . FIG. 32shows that the electro-stimulation circuits may be attached to thefabric cover 315 through the welding of the thermoplastic polymer layer302 of the electro-stimulation circuits and the thermoplastic polymerlayer 321 of the fabric cover 315.

The welding of the thermoplastic polymer layer 302 of theelectro-stimulation circuits and the thermoplastic polymer layer 321 ofthe fabric cover 315 may be performed through a hot plate weldingprocess. Alternatively, this welding may be performed through anultrasound welding process. In further alternative implementations, thiswelding may be performed through a radio frequency welding process.

A radio frequency welding process is based on generating ahigh-frequency electric flux across the thermoplastic polymer layers tobe welded while they are kept together under pressure between anElectrode and a counter-Electrode metallic plate. This electric flux maycause the vibration of the inner molecules of both thermoplastic polymerlayers, and said vibration may cause a local temperature increase at thecontact interface existing between the two layers to be welded.

Therefore, an advantageous aspect of using a radio frequency weldingprocess may be that it may effectively avoid the appearance of creases,fissures and/or deformations on the outer surface of the materials to bewelded. This may be due to that the radio frequency welding process onlyapplies heat at the specific contact interface between the two layers tobe welded, while the rest of the layers are kept at room temperature.

The multilayer fabric cover 315 is shown comprising corresponding holes3110, 3113 through which skin friendly current transmissions can occurbetween the electrode portions 319, 3112 and the skin of the patient. Ascommented before, the electrically conductive layer 303, which may bemade of carbon fibre, and/or metallic mesh, and/or any other materialsuitable for the intended aim(s), may be connected with correspondingconductive wires comprised in the hybrid tube 316.

FIG. 32 further shows corresponding regions 318′, 3111′ of the trackportions 318, 3111 respectively and their attachment with the fabriccover 315 of the pressure cuff 310 through corresponding thermoplasticpolymer layers 302, 321.

Any of the principles used for constructing electro-stimulation circuitsdescribed in relation to FIGS. 30a -32 can be used for fabricating anyof the pressure cuffs described with reference to FIGS. 27a -29 b.

Although only a number of examples have been disclosed herein, otheralternatives, modifications, uses and/or equivalents thereof arepossible. Furthermore, all possible combinations of the describedexamples are also covered. Thus, the scope of the present disclosureshould not be limited by the particular examples.

Clause 1. A method is provided for automated determination of aneuromuscular blockade status for a patient to whom a muscle relaxanthas been delivered, wherein

a plurality of neuromuscular blockade statuses are predefined, and foreach of the neuromuscular blockade statuses are predefined

one or more stimulation cycles with a cycle periodicity and one or morecriterions for changing from the neuromuscular blockade status toanother neuromuscular blockade status, said criterions including a firstcriterion or first set of criterions for changing the neuromuscularblockade status to a first other neuromuscular blockade status;

the method comprising:

automatically performing one or more stimulation cycles predefined forthe neuromuscular blockade status;

automatically determining one or more muscle responses to at least someof the performed stimulation cycles;

automatically comparing the muscle responses with the predefinedcriterions for changing the neuromuscular blockade status; and

if the muscle responses fulfil the predefined first criterion or firstset of criterions, then

automatically performing one or more stimulation cycles predefined forthe first other neuromuscular blockade status.

Clause 2. A method according to clause 1, wherein for one or more of theneuromuscular blockade statuses, the one or more criterions for changingfrom the neuromuscular blockade status to another neuromuscular blockadestatus further comprise:

a second criterion or second set of criterions for changing theneuromuscular blockade status to a second other neuromuscular blockadestatus; wherein

if the muscle responses fulfil the predefined second criterion or secondset of criterions, then

automatically performing one or more stimulation cycles predefined forthe second other neuromuscular blockade status.

Clause 3. A method according to any of clauses 1 or 2, wherein theplurality of neuromuscular blockade statuses comprises an inductionstatus, a moderate status, a deep status, an intense status, andoptionally a reversion status and an end-of-reversion status.

Clause 4. A method according to clause 3, wherein the one or morepredefined stimulation cycles comprise a predefined stimulation cycleaccording to a Single Twitch (ST) pattern based on generating a singleST stimulation pulse, such that

a muscle response to a performed ST stimulation cycle has a single STresponse pulse induced by the ST stimulation pulse, and

a ST-ratio parameter corresponding to the percentage of the ST responsepulse with respect to a ST response pulse of reference determined beforedelivering the muscle relaxant to the patient.

Clause 5. A method according to clause 4, wherein the induction statushas the ST stimulation cycle predefined with a cycle periodicity in arange of 0.5-2 seconds, and preferably equal to approximately 1 second.

Clause 6. A method according to clause 5, wherein the first set ofcriterions of the induction status comprises an ST-ratio of the STstimulation cycle for changing the neuromuscular blockade status fromthe induction status to the moderate status.

Clause 7. A method according to clause 3, wherein the one or morepredefined stimulation cycles comprise a predefined stimulation cycleaccording to a Train of four (TOF) pattern based on generating first,second, third and fourth TOF stimulation pulses, such that

a muscle response to a performed TOF stimulation cycle has first,second, third and fourth TOF response pulses induced by the first,second, third and fourth TOF stimulation pulses respectively,

a TOF-count parameter corresponding to the number of TOF response pulseswith amplitude greater than zero in the TOF muscle response, and

a TOF-ratio parameter corresponding to the percentage of the fourth TOFresponse pulse with respect to the first TOF response pulse.

Clause 8. A method according to clause 7, wherein the induction statushas the TOF stimulation cycle predefined with a cycle periodicity in arange of 8-20 seconds, preferably equal to approximately 12 seconds.

Clause 9. A method according to clause 8, wherein the first set ofcriterions of the induction status comprises a TOF-count less than 4, inwhich case the neuromuscular blockade status is changed from theinduction status to the moderate status.

Clause 10. A method according to any of clauses 8 or 9, wherein thefirst set of criterions of the induction status comprises

a TOF-ratio less than between 25% and 35%, and preferably less than 30%,during between 3 and 7 minutes, and preferably during 5 minutes,

in which case the neuromuscular blockade status is changed from theinduction status to the moderate status.

Clause 11. A method according to any of clauses 8 to 10, wherein thefirst set of criterions of the induction status comprises

the neuromuscular blockade status having been the induction statusduring between 12 and 18 minutes, and preferably during approximately 15minutes,

in which case the neuromuscular blockade status is changed from theinduction status to an unblocked status.

Clause 12. A method according to any of clauses 7 to 11, wherein themoderate status has the TOF stimulation cycle predefined with a cycleperiodicity in a range of 30 seconds-2 minutes, and preferably equal toapproximately 1 minute.

Clause 13. A method according to clause 12, wherein the first set ofcriterions of the moderate status comprises

whether two consecutive TOF-counts are equal to 0,

in which case the neuromuscular blockade status is changed from themoderate status to the deep status.

Clause 14. A method according to any of clauses 12 or 13, wherein thefirst set of criterions of the moderate status comprises

a TOF-ratio greater than or equal to between 2% and 6%, and preferablygreater than or equal to approximately 4%,

in which case the neuromuscular blockade status is changed from themoderate status to the reversion status.

Clause 15. A method according to any of clauses 12 to 14, wherein thefirst set of criterions of the moderate status comprises

a TOF-ratio greater than or equal to between 75% and 85%, and preferablygreater than or equal to approximately 80%,

in which case the neuromuscular blockade status is changed from themoderate status to the end-of-reversion status.

Clause 16. A method according to any of clauses 12 to 15, wherein thefirst set of criterions of the moderate status comprises

a TOF-ratio greater than or equal to between 40% and 60%, and preferablygreater than or equal to approximately 50%,

in which case the neuromuscular blockade status is changed from themoderate status to the reversion status.

Clause 17. A method according to any of clauses 12 to 16, wherein thefirst set of criterions of the moderate status comprises

a TOF-ratio greater than or equal to X %+MIN-TOF-ratio,

in which case the neuromuscular blockade status is changed from themoderate status to the reversion status;

wherein X % is in a range of 20%-30%, and preferably equal toapproximately 25%, and MIN-TOF-ratio is the smallest TOF-ratiodetermined during the moderate status.

Clause 18. A method according to any of clauses 7 to 17, wherein thereversion status has the TOF stimulation cycle predefined with a cycleperiodicity in a range of 30 seconds-1 minute, and preferably equal toapproximately 1 minute.

Clause 19. A method according to clause 18, wherein the first set ofcriterions of the reversion status comprises

a TOF-ratio greater than or equal to between 75% and 85%, and preferablygreater than or equal to approximately 80%,

in which case the neuromuscular blockade status is changed from thereversion status to the end-of-reversion status.

Clause 20. A method according to any of clauses 18 or 19, wherein thefirst set of criterions of the reversion status comprises

two consecutive TOF-counts are less than 4,

in which case the neuromuscular blockade status is changed from thereversion status to the moderate status.

Clause 21. A method according to any of clauses 18 to 20, wherein thefirst set of criterions of the reversion status comprises

four TOF-counts less than between 25% and 35%, and preferably less thanapproximately 30%,

in which case the neuromuscular blockade status is changed from thereversion status to the moderate status.

Clause 22. A method according to any of clauses 7 to 21, wherein theend-of-reversion status has the TOF stimulation cycle predefined with acycle periodicity in a range of 20-40 seconds, and preferably equal toapproximately 30 seconds.

Clause 23. A method according to clause 22, wherein the first set ofcriterions of the end-of-reversion status comprises

a TOF-ratio less than between 55% and 65%, and preferably less thanapproximately 60%,

in which case the neuromuscular blockade status is changed from theend-of-reversion status to the reversion status.

Clause 24. A method according to any of clauses 22 or 23, wherein thefirst set of criterions of the end-of-reversion status comprises

two consecutive TOF-counts less than 4,

in which case the neuromuscular blockade status is changed from theend-of-reversion status to the moderate status.

Clause 25. A method according to any of clauses 22 to 24, wherein thefirst set of criterions of the end-of-reversion status comprises

four TOF-ratios less than between 25% and 35%, and preferably less thanapproximately 30%,

in which case the neuromuscular blockade status is changed from theend-of-reversion status to the moderate status.

Clause 26. A method according to any of clauses 22 to 25, wherein thefirst set of criterions of the end-of-reversion status comprises

a TOF-ratio counter greater than or equal to 5,

in which case the neuromuscular blockade status is changed from theend-of-reversion status to an unblocked status;

wherein said TOF-ratio counter is calculated based on the followingrules:

initializing the counter=0;

if 91%≤TOF-ratio≤94%, adding 1 to the counter;

if 95%≤TOF-ratio≤98%, adding 2 to the counter;

if TOF-ratio≥99%, adding 3 to the counter.

Clause 27. A method according to any of clauses 7 to 26, wherein thedeep status has the TOF stimulation cycle predefined with a cycleperiodicity in a range of 1-5 minutes, and preferably equal toapproximately 2 minutes.

Clause 28. A method according to any of clauses 7 to 26, wherein thedeep status has the TOF stimulation cycle predefined with a cycleperiodicity in a range of 20-40 seconds, and preferably equal toapproximately 30 seconds.

Clause 29. A method according to any of clauses 27 or 28, wherein thefirst set of criterions of the deep status comprises

a TOF-count greater than zero,

in which case the neuromuscular blockade status is changed from the deepstatus to the moderate status.

Clause 30. A method according to any of clauses 27 to 29, wherein thefirst set of criterions of the deep status comprises

a TOF-ratio greater than or equal to between 5% and 9%, and preferablyequal to approximately 7%,

in which case the neuromuscular blockade status is changed from the deepstatus to the reversion status.

Clause 31. A method according to any of clauses 27 to 30, wherein thefirst set of criterions of the deep status comprises

a TOF-ratio greater than or equal to between 75% and 85%, and preferablyequal to approximately 80%,

in which case the neuromuscular blockade status is changed from the deepstatus to the end-of-reversion status.

Clause 32. A method according to any of clauses 7 to 31, wherein theintense status has the TOF stimulation cycle predefined with a cycleperiodicity in a range of 2-5 minutes, and preferably equal toapproximately 2 minutes.

Clause 33. A method according to any of clauses 7 to 31, wherein theintense status has the TOF stimulation cycle predefined with a cycleperiodicity in a range of 20-40 seconds, and preferably equal toapproximately 30 seconds.

Clause 34. A method according to any of clauses 32 or 33, wherein thefirst set of criterions of the intense status comprises

a TOF-count greater than zero,

in which case the neuromuscular blockade status is changed from theintense status to the moderate status.

Clause 35. A method according to any of clauses 32 to 34, wherein thefirst set of criterions of the intense status comprises

a TOF-ratio greater than or equal to between 5% and 15%, and preferablygreater than or equal to approximately 10%,

in which case the neuromuscular blockade status is changed from theintense status to the reversion status.

Clause 36. A method according to any of clauses 32 to 35, wherein thefirst set of criterions of the intense status comprises

a TOF-ratio greater than or equal to between 75% and 85%, and preferablyequal to approximately 80%,

in which case the neuromuscular blockade status is changed from theintense status to the end-of-reversion status.

Clause 37. A method according to any of clauses 7 to 36 and to clause 2,wherein the one or more predefined stimulation cycles further comprise apredefined stimulation cycle according to a Post-tetanic count (PTC)pattern based on a tetanus stimulation during between 2 and 8 seconds,and preferably during approximately 5 seconds, followed by a period ofsingle twitch (ST) pulses of between 10 and 20 seconds, and preferablyof approximately 15 seconds, such that

a muscle response to a performed PTC stimulation cycle has PTC responsepulses induced by the ST pulses of the PTC stimulation cycle, and

a FTC-count parameter corresponding to the number of PTC response pulseswith amplitude greater than zero in the PTC muscle response.

Clause 38. A method according to clause 37, wherein each of the deepstatus and intense status has the PTC stimulation cycle predefined witha cycle periodicity in a range of 6-15 minutes, and preferably equal toapproximately 6 minutes.

Clause 39. A method according to any of clauses 37 or 38, wherein thesecond set of criterions of the deep status comprises

a FTC-count less than or equal to between 3 and 5, and preferably lessthan or equal to approximately 4,

in which case the neuromuscular blockade status is changed from the deepstatus to the intense status.

Clause 40. A method according to any of clauses 37 to 39, wherein thesecond set of criterions of the intense status comprises

a PTC-count greater than or equal to between 6 and 10, and preferablygreater than or equal to approximately 8,

in which case the neuromuscular blockade status is changed from theintense status to the deep status.

Clause 41. A method according to any of clauses 4 to 40, wherein:

the one or more muscle responses are determined through a pressure cuffapplied to the patient, such that any muscle response has a form of apressure wave representative of how pressure varies over time in thecuff as a result of a muscle reaction to corresponding performedstimulation cycle.

Clause 42. A method according to clause 41, further comprising:

determining the end of a heartbeat of the patient; and

wherein the first TOF stimulation pulse is generated substantially atthe end of the heartbeat of the patient.

Clause 43. A method according to clause 42, further comprising:

determining a first characteristic indicative of the shape of the upwardslope of the first TOF response pulse; and

for at least some further TOF response pulse included in the second,third and fourth TOF response pulses:

determining the first characteristic of the further TOF response pulse;

determining a deviation between the first characteristic of the furtherTOF response pulse and the first characteristic of the first TOFresponse pulse;

verifying if the deviation exceeds a deviation threshold, and,

in case of a negative result of the verification, adjusting the furtherTOF response pulse by assuming that the time until peak of the furtherTOF response pulse is measured correctly and that the shape of itsupward slope can be described by the first characteristic of the firstTOF response pulse.

Clause 44. A method according to clause 43, further comprising:

in case of a positive result of the verification, adjusting the furtherTOF response pulse either based on a first assumption that the timeuntil peak of the further TOF response pulse is measured correctly andthat the shape of its upward slope can be described by the firstcharacteristic of the first TOF response pulse, or based on

a second assumption that the time until peak of the further TOF responsepulse is measured correctly and that the shape of its upward slope canbe described by substantially subtracting a heartbeat pulse of referencefrom the further TOF response pulse.

Clause 45. A method is provided for determining a muscle response to anelectro-stimulation of the muscle in a patient, the method comprising:

determining the end of a heartbeat of the patient;

performing the electro-stimulation of the muscle by causing generationof a first electro-stimulation pulse and, subsequently, one or morefurther electro-stimulation pulses, the first electro-stimulation pulsebeing generated substantially at the end of the heartbeat;

determining the muscle response in the form of a pressure waverepresenting how pressure varies over time in a pressure cuff as amuscle reaction to the electro-stimulation, the pressure wave comprisingfirst and further pressure pulses induced by the first and furtherelectro-stimulation pulses respectively;

determining a first characteristic indicative of the shape of the upwardslope of the first pressure pulse; and

for at least some of the further pressure pulses:

determining the first characteristic of the further pressure pulse;

determining a deviation between the first characteristic of the furtherpressure pulse and the first characteristic of the first pressure pulse;

verifying if the deviation exceeds a deviation threshold, and,

In case of a negative result of the verification, adjusting the furtherpressure pulse by assuming that the time until peak of the furtherpressure pulse is measured correctly and that the shape of its upwardslope can be described by the first characteristic of the first pressurepulse.

Clause 46. A method according to clause 45, wherein the at least some ofthe further pressure pulses comprises all the further pressure pulses ofthe pressure wave.

Clause 47. A method according to any of clauses 45 or 46, wherein thefirst characteristic of a pressure pulse is determined depending on anamplitude of the pressure pulse and a maximum derivative of the upwardslope of the pressure pulse.

Clause 48. A method according to clause 47, wherein the firstcharacteristic of the pressure pulse is determined based on thefollowing formula:

${C({pulse})} = \frac{A({pulse})}{d_{\max}({pulse})}$

wherein: C(pulse) is the first characteristic of the pressure pulse,A(pulse) is the amplitude of the pressure pulse, and d_(max)(pulse) isthe maximum derivative of the upward slope of the pressure pulse.

Clause 49. A method according to clause 48, wherein adjusting thefurther pressure pulse comprises:

adjusting an amplitude of the further pressure pulse based on thefollowing formula:A _(adjusted)(further_pulse)=C(first_pulse)×d _(max)(further_pulse)

wherein: A_(adjusted)(further_pulse) is the adjusted amplitude of thefurther pressure pulse, C(first_pulse) is the first characteristic ofthe first pressure pulse, and d_(max)(further_pulse) is the maximumderivative of the upward slope of the further pressure pulse.

Clause 50. A method according to any of clauses 44 to 48, wherein thedeviation threshold is in a range of 10%-20%, preferably equal to 15%.

Clause 51. A method according to any of clauses 45 to 50, furthercomprising:

in case of a positive result of the verification, adjusting the furtherpressure pulse either based on a first assumption that the time untilpeak of the further pressure pulse is measured correctly and that theshape of its upward slope can be described by the first characteristicof the first pressure pulse, or based on

a second assumption that the time until peak of the further pressurepulse is measured correctly and that the shape of its upward slope canbe described by substantially subtracting a heartbeat pulse of referencefrom the measured further pressure pulse.

Clause 52. A method according to clause 51, wherein adjusting thefurther pressure pulse based on the first assumption comprises:

determining a first adjusted amplitude of the further pressure pulsebased on the first assumption.

Clause 53. A method according to clause 52, wherein the first adjustedamplitude of the further pressure pulse is determined based on thefollowing formula:A _(adjusted)(further_pulse)=C(first_pulse)×d _(max)(further_pulse)

wherein: A_(adjusted)(further_pulse) is the first adjusted amplitude ofthe further pressure pulse, C(first_pulse) is the first characteristicof the first pressure pulse, and d_(max)(further_pulse) is the maximumderivative of the upward slope of the further pressure pulse.

Clause 54. A method according to any of clauses 51 to 53, whereinadjusting the further pressure pulse based on the second assumptioncomprises:

determining a second adjusted amplitude of the further pressure pulsebased on the second assumption.

Clause 55. A method according to clause 54, wherein the second adjustedamplitude of the further pressure pulse is determined depending on asecond characteristic of the shape of the upward slope of the heartbeatpulse of reference.

Clause 56. A method according to clause 55, wherein the secondcharacteristic is determined depending on an amplitude of the heartbeatpulse of reference and a time until peak of the heartbeat pulse ofreference.

Clause 57. A method according to clause 56, wherein the secondcharacteristic is determined based on the following formula:

${C\left( {{hb\_}{pulse}} \right)} = \frac{A({hb\_ pulse})}{t_{S}({hb\_ pulse})}$

wherein: C(hb_pulse) is the second characteristic of the heartbeat pulseof reference, A(hb_pulse) is the amplitude of the heartbeat pulse ofreference, and t_(S)(hb_pulse) is the time until peak of the heartbeatpulse of reference.

Clause 58. A method according to any of clauses 54 to 57, wherein thesecond adjusted amplitude of the further pressure pulse is determinedfurther depending on the amplitude of the further pressure pulse and thetime until peak of the further pressure pulse.

Clause 59. A method according to clause 58, wherein the second adjustedamplitude of the further pressure pulse is determined based on thefollowing formula:A _(adjusted)(further_pulse)=A(further_pulse)−t_(S)(further_pulse)×C(hb_pulse)

wherein: A_(adjusted)(further_pulse) is the second adjusted amplitude ofthe further pressure pulse, A(further_pulse) is the amplitude of thefurther pressure pulse, t_(S)(further_pulse) is the time until peak ofthe further pressure pulse, and C(hb_pulse) is the second characteristicof the heartbeat pulse of reference.

Clause 60. A method according to any of clauses 52 or 53 and to any ofclauses 54 to 59, wherein adjusting the further pressure pulse eitherbased on the first assumption or based on the second assumptioncomprises:

adjusting the amplitude of the further pressure pulse by selecting thesmaller of the first and second adjusted amplitudes.

Clause 61. A method according to any of clauses 45 to 60, wherein:

the electro-stimulation is performed according to a Train of four (TOF)pattern which is based on generating a first electro-stimulation pulseand three further electro-stimulation pulses; and wherein:

determining the muscle response further comprises determining aTOF-ratio parameter corresponding to a relation between the amplitude ofone of the three further pressure pulses and the amplitude of the firstpressure pulse.

Clause 62. A method according to clause 61, wherein determining theTOF-ratio parameter comprises:

verifying thatA(first_pulse)≥A(second_pulse)≥A(third_pulse)≥A(fourth_pulse), in whichcase, the TOF-ratio parameter is the percentage of the fourth_pulse withrespect to the first_pulse; wherein:

first_pulse is the first pulse in the pressure wave, and A(first_pulse)is the amplitude of said first pulse;

fourth_pulse is the fourth pulse in the pressure wave, andA(fourth_pulse) is the amplitude of said fourth pulse;

A(second_pulse) is the amplitude of the second pulse in the pressurewave; and

A(third_pulse) is the amplitude of the third pulse in the pressure wave.

Clause 63. A method according to any of clauses 61 or 62, whereindetermining the TOF-ratio parameter comprises:

verifying thatA(first_pulse)≥A(second_pulse)≥A(third_pulse)<A(fourth_pulse), in whichcase, the TOF-ratio parameter is determined based on the followingformula:

${TOF}_{RATIO} = \left( \frac{A({third\_ pulse})}{A({first\_ pulse})} \right)^{X}$

wherein:

TOF_(RATIO) is the TOF-ratio parameter;

A(first_pulse) is the amplitude of the first pulse in the pressure wave;

A(second_pulse) is the amplitude of the second pulse in the pressurewave;

A(third_pulse) is the amplitude of the third pulse in the pressure wave;

A(fourth_pulse) is the amplitude of the fourth pulse in the pressurewave; and

X is a value used to compensate that the TOF-ratio parameter iscalculated depending on the amplitude of the first and third pulsesrather than on the amplitude of the first and fourth pulse.

Clause 64. A method according to any of clauses 61 to 63, whereindetermining the TOF-ratio parameter comprises:

verifying thatA(first_pulse)≥A(second_pulse)<A(third_pulse)<A(fourth_pulse), in whichcase, the TOF-ratio parameter is determined based on the followingformula:

${TOF}_{RATIO} = \left( \frac{A({second\_ pulse})}{A({first\_ pulse})} \right)^{Y}$

wherein:

TOF_(RATIO) is the TOF-ratio parameter;

A(first_pulse) is the amplitude of the first pulse in the pressure wave;

A(second_pulse) is the amplitude of the second pulse in the pressurewave;

A(third_pulse) is the amplitude of the third pulse in the pressure wave;

A(fourth_pulse) is the amplitude of the fourth pulse in the pressurewave; and

Y is a value used to compensate that the TOF-ratio parameter iscalculated depending on the amplitude of the first and second pulsesrather than the amplitude of the first and fourth pulses.

Clause 65. An electro-stimulation electrode configured to be applieddryly on the skin of a patient, comprising:

a support layer made of an electrically insulating material and havingat least one region with one or more holes, wherein a first surface ofthe support layer is arranged in such a way that, in use, it contactsthe patient's skin;

an electrically conductive medium adhered to a second surface of thesupport layer, opposite to the first surface, and arranged completely orpartially surrounding the region with holes in such a way that theelectrically conductive medium does not cover the region with holes; and

a first conductive layer contacting the electrically conductive mediumin such a way that the first conductive layer covers the region withholes.

Clause 66. An electro-stimulation electrode according to clause 65,wherein the first conductive layer is made of a conductive composite oran intrinsically conductive polymer.

Clause 67. An electro-stimulation electrode according to any of clauses65 or 66, wherein the electrically conductive medium is arranged betweenthe support layer and the first conductive layer.

Clause 68. An electro-stimulation electrode according to clause 67,further comprising a second conductive layer arranged on the firstsurface of the support layer in such a way that the second conductivelayer contacts the first conductive layer through at least one of theholes.

Clause 69. An electro-stimulation electrode according to clause 68,wherein the second conductive layer is made of a conductive composite oran intrinsically conductive polymer.

Clause 70. An electro-stimulation electrode according to any of clauses68 or 69, wherein the second conductive layer has a flat shape, or aconvex shape, or a shape provided with relief at the level of the regionwith the at least one hole.

Clause 71. An electro-stimulation electrode according to any of clauses65 or 66, wherein the first conductive layer is arranged between theelectrically conductive medium and the support layer.

Clause 72. An electro-stimulation electrode according to clause 71,further comprising a second conductive layer arranged between the firstconductive layer and the support layer, said second layer covering atleast one of the holes of the support layer.

Clause 73. An electro-stimulation electrode according to clause 72,wherein the second conductive layer is made of a conductive composite oran intrinsically conductive polymer.

Clause 74. An electro-stimulation electrode according to any of clauses72 or 73, wherein the second conductive layer has a flat shape, or aconvex shape, or a shape provided with relief at the level of the regionwith holes.

Clause 75. An electro-stimulation electrode according to any of clauses72 to 74, further comprising a third conductive layer arranged betweenthe first conductive layer and the second conductive layer, wherein

the third conductive layer has an outline substantially complementary tothe outline of the holes, and the third conductive layer is arrangedcoincident with the holes.

Clause 76. An electro-stimulation electrode according to clause 75,wherein the third conductive layer is made of a conductive composite oran intrinsically conductive polymer.

Clause 77. An electro-stimulation electrode according to any of clauses75 or 76, wherein the first, second and third conductive layers have anaggregate thickness in a range of 160-200 microns.

Clause 78. An electro-stimulation electrode according to any of clauses71 to 77, further comprising an inner covering layer having an outlineexceeding the first and second conductive layers.

Clause 79. An electro-stimulation electrode according to any of clauses65 to 78, wherein the support layer is a nylon fabric or a paper fabricor a nonwoven fabric.

Clause 80. An electro-stimulation electrode according to any of clauses65 to 79, wherein the electrically conductive medium is an electricallyconductive track or cable.

Clause 81. An electro-stimulation electrode according to clause 80,wherein the electrically conductive track is an electrically conductivemetallic fabric or a printed electrically conductive ink.

Clause 82. An electro-stimulation electrode according to any of clauses65 to 81, wherein the electrically conductive medium completelysurrounds the region with holes.

Clause 83. A pressure cuff comprising at least an electro-stimulationelectrode according to any of clauses 65 to 82.

Clause 84. A hybrid air-signal connector is provided for connecting anair-signal tube to an electro-stimulation cuff, the hybrid air-signalconnector comprising

a main body having a base with a first tubular portion arranged on afirst face of the base in such a way that, in use, the first tubularportion is fitted into an air conduit of the air-signal tube such thatair can flow between the air conduit and the inside of the cuff throughthe first tubular portion; and

two connection electrodes which are either L-shaped or substantiallyflat, each having

an external terminal arranged in such a way that, in use, the externalterminal contacts an electrically conductive cable of the air-signaltube, and

an internal terminal embedded in the base with an end portion arrangedon the first face of the base in such a way that, in use, this endportion contacts an inner conductive track of the cuff when the hybridair-signal connector is introduced into a connection bore of the cuff;wherein

in the case of the L-shaped connection electrodes, the externalterminals extend from the base parallel to the first tubular portion, or

in the case of the substantially flat connection electrodes, theexternal terminals are embedded in the base.

Clause 85. A hybrid air-signal connector according to clause 84,comprising a second tubular portion outwardly coaxially arranged withrespect to the first tubular portion in such a way that, in use, thesecond tubular portion protects the external terminals, acts as a guidefor connecting the air-signal tube to the air-signal connector, andavoids the intrusion of liquids and/or dust in said connection.

Clause 86. A hybrid air-signal connector according to clause 85, whereinthe second tubular portion has a length smaller than the length of thefirst tubular portion.

Clause 87. A hybrid air-signal connector according to any of clauses 84to 86, which is constituted by only three single bodies: the main bodyand the two electrodes.

Clause 88. A hybrid air-signal connector according to any of clauses 84to 87, wherein, in the case of the L-shaped electrodes, the externalterminals have a cylindrical shape and the internal terminals aresubstantially flat.

Clause 89. A hybrid air-signal connector according to any of clauses 84to 88, wherein the base comprises a central ring configured to providepneumatic air tightness, and wherein the central ring protrudes withrespect to the first face of the base.

Clause 90. A hybrid air-signal connector according to any of clauses 84to 89, comprising at the face of the base opposite to the first faceholes for accessing to the end portions of the internal terminals.

Clause 91. A hybrid air-signal connector according to any of clauses 84to 90, wherein the electrodes are asymmetrically arranged.

Clause 92. A hybrid air-signal connector according to any of clauses 84to 91, wherein the main body is made of polyurethane.

Clause 93. A hybrid air-signal connector according to any of clauses 84to 92, wherein the base has a substantially elliptical shape.

Clause 94. A hybrid air-signal connector according to any of clauses 84to 93, wherein:

the first tubular portion has a length of approximately 16 mm and adiameter of approximately 3 mm;

the external terminals have, in the case of the L-shaped electrodes, alength of approximately 7 mm and a diameter of approximately 1 mm;

the external terminals have, in the case of the flat electrodes, a widthof approximately 1.5 mm;

the internal terminals have a width of approximately 1.5 mm;

the second tubular portion has a length of approximately 12 mm;

the base is elliptical with an axis of approximately 23 mm and anotheraxis of approximately 28 mm;

the ring for pneumatic air tightness has a diameter of approximately 16mm;

the end portions of the internal terminals have a length ofapproximately 4 mm.

Clause 95. A pressure cuff comprising a hybrid air-signal connectoraccording to any of clauses 84 to 94.

Clause 96. A pressure cuff is provided that is configured to be arrangedaround a limb of a patient, the pressure cuff comprising an activeelectro-stimulation electrode and a passive electro-stimulationelectrode; wherein

the active electro-stimulation electrode is configured to transmit anelectrical current and arranged in the pressure cuff in such a way that,in use, a contact surface of the active electro-stimulation electrode isarranged on a first region of the limb, which is at least partially on aperipheral motor nerve of the limb such that the nerve receives at leastpart of the transmitted electrical current; wherein

the passive electro-stimulation electrode is configured to collect anelectrical current and arranged in the pressure cuff in such a way that,in use, a contact surface of the passive electro-stimulation electrodeis arranged on a second region of the limb, such that the transmittedelectrical current is collected by the passive electro-stimulationelectrode; and wherein the second region of the limb is not on theperipheral motor nerve of the limb, and/or

the contact surface of the passive electro-stimulation electrode issubstantially larger in size than the contact surface of the activeelectro-stimulation electrode.

Clause 97. A pressure cuff according to clause 96, wherein the secondregion of the limb is at least partially on the peripheral motor nerveof the limb; and wherein

the contact surface of the passive electro-stimulation electrode issubstantially larger in size than the contact surface of the activeelectro-stimulation electrode.

Clause 98. A pressure cuff according to clause 97, wherein the contactsurface of the passive electro-stimulation electrode substantiallycompletely surrounds the contact surface of the activeelectro-stimulation electrode.

Clause 99. A pressure cuff according to clause 98, wherein the contactsurface of the passive electro-stimulation electrode substantiallycompletely surrounds the contact surface of the activeelectro-stimulation electrode in a substantially coaxial manner.

Clause 100. A pressure cuff according to clause 97, wherein the contactsurface of the passive electro-stimulation electrode partially surroundsthe contact surface of the active electro-stimulation electrode.

Clause 101. A pressure cuff according to clause 100, wherein the contactsurface of the passive electro-stimulation electrode partially surroundsthe contact surface of the active electro-stimulation electrode in asubstantially coaxial manner.

Clause 102. A pressure cuff according to any of clauses 100 or 101,wherein the contact surface of the passive electro-stimulation electrodeis substantially C-shaped.

Clause 103. A pressure cuff according to clause 96, wherein the secondregion of the limb is not on the peripheral motor nerve; and wherein

the contact surface of the passive electro-stimulation electrode issubstantially larger in size than the contact surface of the activeelectro-stimulation electrode.

Clause 104. A pressure cuff according to clause 103, wherein the contactsurface of the passive electro-stimulation electrode partially surroundsthe contact surface of the active electro-stimulation electrode.

Clause 105. A pressure cuff according to clause 104, wherein the contactsurface of the passive electro-stimulation electrode partially surroundsthe contact surface of the active electro-stimulation electrode in asubstantially coaxial manner.

Clause 106. A pressure cuff according to any of clauses 104 or 105,wherein the contact surface of the passive electro-stimulation electrodeis formed as two annular segments each having a first end and a secondend, the first ends facing each other with a first gap in between andthe second ends facing each other with a second gap in between.

Clause 107. A pressure cuff according to any of clauses 96 to 106,wherein the active electro-stimulation electrode is a first electrodeportion of a first electro-stimulation circuit, and the passiveelectro-stimulation electrode is a second electrode portion of a secondelectro-stimulation circuit; wherein

the first electro-stimulation circuit further comprises a first trackportion for conducting the electrical current to the first electrodeportion, and the second electro-stimulation circuit further comprises asecond track portion for conducting the electrical current from thesecond electrode portion; wherein

the first electrode and track portions are integrally formed as a singlemultilayer film comprising a layer of thermoplastic polymer doped withelectrically conductive particles and a layer of electrically conductivematerial, said layers being attached to each other; and wherein

the second electrode and track portions are integrally formed as asingle multilayer film comprising a layer of thermoplastic polymer dopedwith electrically conductive particles and a layer of electricallyconductive material, said layers being attached to each other.

Clause 108. A pressure cuff according to clause 107, wherein each of thefirst and second electro-stimulation circuits is attached to thepressure cuff by radio frequency welding of a layer of theelectro-stimulation circuit made of thermoplastic polymer to a region ofthe pressure cuff made of thermoplastic polymer.

Clause 109. An electro-stimulation circuit is provided that comprises

an electrode portion configured to either transmit or collect anelectrical current to/from a region of a patient for electro-stimulatinga nerve, and

a track portion for conducting the electrical current to/from theelectrode portion; wherein

the electrode and track portions are integrally formed as a singlemultilayer film having a plurality of layers; and wherein

the plurality of layers comprises a first layer of thermoplastic polymerdoped with electrically conductive particles and a second layer ofelectrically conductive material, the first layer and the second layerbeing attached to each other.

Clause 110. An electro-stimulation circuit according to clause 109,wherein

the plurality of layers further comprises a third layer of thermoplasticpolymer attached to the second layer in such a way that the second layeris sandwiched between the first layer and the third layer.

Clause 111. An electro-stimulation circuit according to clause 110,wherein the third layer is made of thermoplastic polymer doped withelectrically conductive particles.

Clause 112. An electro-stimulation circuit according to any of clauses109 to 111, wherein the layers of the plurality of layers are attachedtogether with a heated lamination process.

Clause 113. An electro-stimulation circuit according to any of clauses109 to 112, wherein the thermoplastic polymer comprises Thermoplasticpolyurethane (TPU).

Clause 114. An electro-stimulation circuit according to any of clauses109 to 113, wherein the thermoplastic polymer comprises Polyvinylchloride (PVC).

Clause 115. An electro-stimulation circuit according to any of clauses109 to 114, wherein the electrically conductive particles are graphiteparticles.

Clause 116. An electro-stimulation circuit according to any of clauses109 to 115, wherein the second layer comprises an electricallyconductive fabric.

Clause 117. An electro-stimulation circuit according to clause 116,wherein the electrically conductive fabric is at least partially made ofcarbon fibre.

Clause 118. An electro-stimulation circuit according to any of clauses116 or 117, wherein the electrically conductive fabric is at leastpartially made of metallic mesh.

Clause 119. A pressure cuff configured to be arranged around a limb of apatient, the pressure cuff comprising at least one electro-stimulationcircuit according to any of clauses 109 to 118; wherein

the electro-stimulation circuit is attached to the pressure cuff in sucha way that, in use, a contact surface of the electrode portion of theelectro-stimulation circuit is arranged on a region of the limb, suchthat an electrical current can be either transmitted or collected by theelectrode portion to/from said region of the limb forelectro-stimulating a peripheral motor nerve of the limb.

Clause 120. A pressure cuff according to clause 119, wherein theattachment of the electro-stimulation circuit to the pressure cuffcomprises an attachment of a layer of the electro-stimulation circuitmade of thermoplastic polymer to a region of the pressure cuff made ofthermoplastic polymer.

Clause 121. A pressure cuff according to clause 120, wherein thepressure cuff comprises a fabric cover having a layer made ofthermoplastic polymer; and wherein

the region of the pressure cuff to which the electro-stimulation circuitis attached is comprised in the layer of the fabric cover made ofthermoplastic polymer.

Clause 122. A pressure cuff according to clause 121, wherein the fabriccover further comprises a layer made of nylon, paper or nonwoven fabricattached to the layer made of thermoplastic polymer.

Clause 123. A pressure cuff according to clause 122, wherein the layersof the fabric cover are attached together with a heated laminationprocess.

Clause 124. A pressure cuff according to any of clauses 120 to 123,wherein the layer of the electro-stimulation circuit made ofthermoplastic polymer is attached to the region of the pressure cuffmade of thermoplastic polymer with a welding process.

Clause 125. A pressure cuff according to clause 124, wherein the weldingprocess is a hot plate welding process.

Clause 126. A pressure cuff according to clause 124, wherein the weldingprocess is an ultrasound welding process.

Clause 127. A pressure cuff according to clause 124, wherein the weldingprocess is a radio frequency welding process.

Clause 128. A pressure cuff according to any of clauses 119 to 127,wherein

the at least one electro-stimulation circuit comprises an activeelectro-stimulation circuit and a passive electro-stimulation circuit;wherein

the electrode portion of the active electro-stimulation circuit is anactive electro-stimulation electrode, and the electrode portion of thepassive electro-stimulation circuit is a passive electro-stimulationelectrode; wherein

the active electro-stimulation electrode is configured to transmit anelectrical current and arranged in the pressure cuff in such a way that,in use, a contact surface of the active electro-stimulation electrode isarranged on a first region of the limb, which is at least partially on aperipheral motor nerve of the limb such that the nerve receives at leastpart of the transmitted electrical current; wherein

the passive electro-stimulation electrode is configured to collect anelectrical current and arranged in the pressure cuff in such a way that,in use, a contact surface of the passive electro-stimulation electrodeis arranged on a second region of the limb, such that the transmittedelectrical current is collected by the passive electro-stimulationelectrode; and wherein

the second region of the limb is not on the peripheral motor nerve ofthe limb, and/or

the contact surface of the passive electro-stimulation electrode issubstantially larger in size than the contact surface of the activeelectro-stimulation electrode.

Clause 129. A pressure cuff according to clause 128, wherein the trackportion of the active electro-stimulation circuit is connected with theactive electro-stimulation electrode at one end and with an electricitysource at the other end; and wherein

the track portion of the passive electro-stimulation circuit isconnected with the passive electro-stimulation electrode at one end andwith the electricity source at the other end.

Clause 130. An apparatus is provided for determining a muscle responseto an electro-stimulation of the muscle in a patient, the apparatuscomprising:

a pressure cuff configured to be applied around a limb of the patient, acontroller, and a conducting tube connecting the cuff and thecontroller;

wherein the cuff comprises one or more electrodes for electrostimulating a peripheral motor nerve, the electrodes being arranged onthe cuff such that, in use, the electrodes contact the patient's skinwhen the cuff is applied;

wherein the conducting tube is configured to conduct air in such a waythat, in use, the conducting tube propagates air pressure in the cuff tothe controller, and configured to conduct electricity in such a waythat, in use, the conducting tube conveys electrical pulses from thecontroller to the electrodes of the cuff; and

wherein the controller is configured to send one or moreelectro-stimulation pulses to the electrodes, to obtain pressuremeasurements from the cuff as a muscle reaction to theelectro-stimulation pulses, and to determine the muscle response to theelectro-stimulation of the muscle based on the pressure measurements;and

wherein each of the electrodes is either an electro-stimulationelectrode according to any of clauses 65-82.

Clause 131. An apparatus according to clause 130, wherein the conductingtube is connected to the pressure cuff through a hybrid air-signalconnector according to any of clauses 84-94.

Clause 132. An apparatus according to any of clauses 130 or 131, whereinthe pressure cuff is a pressure cuff according to any of clauses 96 to106.

Clause 133. An apparatus is provided for determining a muscle responseto an electro-stimulation of the muscle in a patient, the apparatuscomprising:

a pressure cuff configured to be applied around a limb of the patient, acontroller, and a conducting tube connecting the cuff and thecontroller;

wherein the cuff comprises one or more electrodes for electrostimulating a muscle nerve, the electrodes being arranged on the cuffsuch that, in use, the electrodes contact the patient's skin when thecuff is applied;

wherein the conducting tube is configured to conduct air in such a waythat, in use, the conducting tube propagates air pressure in the cuff tothe controller, and configured to conduct electricity in such a waythat, in use, the conducting tube conveys electrical pulses from thecontroller to the electrodes of the cuff; and

wherein the controller is configured to send one or moreelectro-stimulation pulses to the electrodes, to obtain pressuremeasurements from the cuff as a muscle reaction to theelectro-stimulation pulses, and to determine the muscle response to theelectro-stimulation of the muscle based on the pressure measurements;and

wherein the pressure cuff is a pressure cuff according to any of clauses119 to 127.

Clause 134. An apparatus according to clause 133, wherein the conductingtube is connected to the pressure cuff through a hybrid air-signalconnector according to any of clauses 84-94.

Clause 135. An apparatus according to any of clauses 133 or 134, whereinthe pressure cuff is further according to any of clauses 96 to 108.

Clause 136. An apparatus is provided for determining a muscle responseto an electro-stimulation of the muscle in a patient, the apparatuscomprising:

a pressure cuff configured to be applied around a limb of the patient, acontroller, and a conducting tube connecting the cuff and thecontroller;

wherein the cuff comprises one or more electrodes for electrostimulating a muscle nerve, the electrodes being arranged on the cuffsuch that, in use, the electrodes contact the patient's skin when thecuff is applied;

wherein the conducting tube is configured to conduct air in such a waythat, in use, the conducting tube propagates air pressure in the cuff tothe controller, and configured to conduct electricity in such a waythat, in use, the conducting tube conveys electrical pulses from thecontroller to the electrodes of the cuff; and

wherein the controller is configured to send one or moreelectro-stimulation pulses to the electrodes, to obtain pressuremeasurements from the cuff as a muscle reaction to theelectro-stimulation pulses, and to determine the muscle response to theelectro-stimulation of the muscle based on the pressure measurements;and

wherein the conducting tube is connected to the pressure cuff through ahybrid air-signal connector according to any of clauses 84-94.

Clause 137. An apparatus according to 136, wherein the pressure cuff isa pressure cuff according to any of clauses 96 to 106.

Clause 138. An apparatus is provided for determining a muscle responseto an electro-stimulation of the muscle in a patient, the apparatuscomprising:

a pressure cuff configured to be applied around a limb of the patient, acontroller, and a conducting tube connecting the cuff and thecontroller;

wherein the cuff comprises one or more electrodes for electrostimulating a muscle nerve, the electrodes being arranged on the cuffsuch that, in use, the electrodes contact the patient's skin when thecuff is applied;

wherein the conducting tube is configured to conduct air in such a waythat, in use, the conducting tube propagates air pressure in the cuff tothe controller, and configured to conduct electricity in such a waythat, in use, the conducting tube conveys electrical pulses from thecontroller to the electrodes of the cuff; and

wherein the controller is configured to send one or moreelectro-stimulation pulses to the electrodes, to obtain pressuremeasurements from the cuff as a muscle reaction to theelectro-stimulation pulses, and to determine the muscle response to theelectro-stimulation of the muscle based on the pressure measurements;and

wherein the pressure cuff is a pressure cuff according to any of clauses96 to 106.

What is claimed is:
 1. A pressure cuff configured to be disposedinterchangeably around a right arm and a left arm of a patient, each ofthe right arm and left arm including a peripheral motor nerve, theperipheral motor nerve having an outer membrane, the pressure cuffcomprising; an active electro-stimulation electrode that is configuredto transmit an electrical current and is arranged in the pressure cuffsuch that when the pressure cuff is disposed around either the right armor the left arm, a contact surface of the active electro-stimulationelectrode is respectively arranged at least partially over theperipheral motor nerve of the right arm and left arm, the activeelectro-stimulation electrode configured to transmit the electricalcurrent to the peripheral motor nerve; and a passive electro-stimulationelectrode that is configured to collect at least a portion of thetransmitted electrical current, the passive electro-stimulationelectrode being arranged in the pressure cuff such that when thepressure cuff is disposed around either the right arm or the left arm,with the contact surface of the active electro-stimulation electroderespectively arranged at least partially over the peripheral motor nerveof right arm and left arm, an entirety of a contact surface of thepassive electro-stimulation electrode is respectively arranged on theright arm and left arm and not over the peripheral motor nerve, suchthat the transmitted electrical current is capable of being collected bythe passive electro-stimulation electrode in a manner that preventshyperpolarization of the outer membrane of the peripheral motor nerve.2. A pressure cuff according to claim 1, wherein the activeelectro-stimulation electrode is a first electrode portion of a firstelectro-stimulation circuit, and the passive electro-stimulationelectrode is a second electrode portion of a second electro-stimulationcircuit; wherein the first electro-stimulation circuit further comprisesa first track portion for conducting the electrical current to the firstelectrode portion, and the second electro-stimulation circuit furthercomprises a second track portion for conducting the electrical currentfrom the second electrode portion; wherein the first electrode and thefirst track portion are integrally formed as a single multilayer filmhaving a first plurality of layers comprising a first layer ofthermoplastic polymer doped with electrically conductive particles and asecond layer of electrically conductive material, said layers beingattached to each other; and wherein the second electrode and the secondtrack portion are integrally formed as a single multilayer film having asecond plurality of layers comprising a first layer of thermoplasticpolymer doped with electrically conductive particles and a second layerof electrically conductive material, said layers being attached to eachother.
 3. A pressure cuff according to claim 2, wherein each of thefirst and second electro-stimulation circuits is attached to thepressure cuff by radio frequency welding of a layer of theelectro-stimulation circuit made of thermoplastic polymer to a region ofthe pressure cuff made of thermoplastic polymer.
 4. A pressure cuffaccording to claim 2, wherein the first plurality of layers furthercomprises a third layer of thermoplastic polymer attached to the secondlayer in such a way that the second layer is sandwiched between thefirst layer and the third layer; and wherein the second plurality oflayers further comprises a third layer of thermoplastic polymer attachedto the second layer in such a way that the second layer is sandwichedbetween the first layer and the third layer.
 5. A pressure cuffaccording to claim 4, wherein the third layer of the first plurality oflayers is made of thermoplastic polymer doped with electricallyconductive particles; and wherein the third layer of the secondplurality of layers is made of thermoplastic polymer doped withelectrically conductive particles.
 6. A pressure cuff according to claim2, wherein the layers of the first plurality of layers are attachedtogether with a heated lamination process; and wherein the layers of thesecond plurality of layers are attached together with a heatedlamination process.
 7. A pressure cuff according to claim 2, wherein thethermoplastic polymer comprises thermoplastic polyurethane (TPU) and/orpolyvinyl chloride (PVC).
 8. A pressure cuff according to claim 2,wherein the electrically conductive particles are graphite particles. 9.A pressure cuff according to claim 1, wherein the pressure cuff has awidth and a length, the length being greater than the width, the activeelectro-stimulation electrode being located at a first location alongthe length of the pressure cuff and the passive electro-stimulationelectrode being located at a second location along the length of thepressure cuff, the first location being different from the secondlocation such that the active and passive electro-stimulation electrodesare not in alignment with one another across the width of the pressurecuff.